Benzoheterocyclic compounds

ABSTRACT

Novel benzoheterocyclic compounds of the formula: ##STR1## wherein R 1  is H, halogen, alkyl, optionally substituted amino, alkoxy; R 2  is H, halogen, alkoxy, phenyialkoxy, OH, alkyl, optionally substituted amino, carbamoyl-alkoxy, optionally substituted amino-alkoxy, optionally substituted benzoyloxy; R 3  is a group: --NR 4  R 5  or --CO--NR 11  R 12  ; R 4  is H, optionally substituted benzoyl, alkyl; R 5  is a group: ##STR2## [R 16  is halogen, optionally substituted alkyl, OH, alkoxy, alkanoyloxy, alkylthio, alkanoyl, carboxy, alkoxycarbonyl, CN, NO 2 , optionally substituted amino, phenyl, cycloalkyl, etc., or a group: --O--A--NR 6  R 7  ; m is 0 to 3], phenyl-alkoxycarbonyl, alkanoyl, phenylalkanoyl, etc.; R 11  is H or alkyl; R 12  is cycloalkyl or optionally substituted phenyl; and W is a group: --(CH 2 ) p  (p is 3 to 5) or --CH═CH--(CH 2 ) q  (q is 1 to 3), the carbon atom of these groups being optionally replaced by O, S, SO, SO 2  or a group: --N(R) 12  and further these groups having optionally 1 to 3 substituents of alkyl, alkoxycarbonyl, carboxy, OH, O, alkanoyloxy, etc., which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

This is a divisional of application No. 07/851,541, filed Mar. 13, 1992,U.S. Pat. No. 5,258,510, which is a continuation-in-part of applicationNo. 07/762,015, filed Jun. 19, 1991, (abandoned).

TECHNICAL FIELD

This invention relates to novel benzoheterocyclic compounds which haveexcellent vasopressin antagonistic activities and are useful asvasodilator, hypotensive agent, water diuretics, platelet aggregationinhibitor.

DISCLOSURE OF THE INVENTION

The benzoheterocyclic compounds of this invention have the followingformula: ##STR3## wherein R¹ is hydrogen atom, a halogen atom, a loweralkyl, an amino having optionally a lower alkyl substituent, or a loweralkoxy,

R² is hydrogen atom, a halogen atom, a lower alkoxy, aphenyl(lower)alkoxy, hydroxy, a lower alkyl, an amino having optionallya lower alkyl substituent, a carbamoyl-substituted lower alkoxy, anamino-substituted lower alkoxy having optionally a lower alkylsubstituent, or a benzoyloxy which has optionally a halogen substituenton the phenyl ring,

R³ is a group of the formula: ##STR4## or a group of the formula:##STR5##

R⁴ is hydrogen atom, a benzoyl which has optionally a halogensubstituent on the phenyl ring, or a lower alkyl,

R⁵ is a group of the formula: ##STR6## [wherein R¹⁶ is a halogen atom; alower alkyl which has optionally a substituent selected from a halogenatom and hydroxy; hydroxy; a lower alkoxy; a lower alkanoyloxy; a loweralkylthio; a lower alkanoyl; carboxy; a lower alkoxycarbonyl; cyano;nitro; an amino which has optionally a substituent selected from a loweralkyl and a lower alkanoyl; phenyl; a cycloalkyl; a loweralkanoyloxy-substituted lower alkoxy; a carboxy-substituted loweralkoxy; a halogen-substituted lower alkoxy; a carbamoyl-substitutedlower alkoxy; a hydroxy-substituted lower alkoxy; a loweralkoxycarbonyl-substituted lower alkoxy; a phthalimido-substituted loweralkoxy; an aminocarbonyl-lower alkoxy having a lower alkyl substituent;or a group of the formula: ##STR7## (A is a lower alkylene, and R⁶ andR⁷ are the same or different and are each hydrogen atom, a lower alkylhaving optionally a hydroxy substituent, a lower alkanoyl, or benzoyl,or R⁶ and R⁷ may bind together with nitrogen atom to which they bond toform a 5- or 6-membered saturated heterocyclic group with or withoutbeing intervened with nitrogen or oxygen atom wherein the heterocyclicgroup has optionally a substituent selected from piperidinyl and a loweralkyl); and m is an integer of 0 to 3], a phenyl-lower alkoxy-carbonyl,a lower alkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl,a cycloalkylcarbonyl, tricyclo[3.3.1.1]-decanylcarbonyl,naphthylcarbonyl, pyridylcarbonyl, furoyl, thenoyl, a phenoxy-loweralkanoyl which phenyl ring has optionally 1 to 3 substituents selectedfrom a lower alkyl, a lower alkoxy and an amino having optionally alower alkanoyl substituent, a phthalimido-substituted lower alkanoyl, alower alkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR8## (wherein R⁸ is hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl), an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR9## (wherein B is a lower alkylene, n is an integer of 0 or 1, andR⁹ and R¹⁰ are the same or different and are each hydrogen atom, a loweralkyl having optionally a hydroxy substituent, a cycloalkyl, aphenyl-lower alkyl, a lower alkanoyl, a lower alkenyl, a phenoxy-loweralkyl, a phenyl which has optionally 1 to 3 substituents selected froman amino-lower alkyl having optionally a lower alkanoyl substituent, alower alkyl, a lower alkoxy and a halogen atom, aphthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with nitrogen atom to which they bond to form a 5-or 6-membered saturated heterocyclic group with or without beingintervened with nitrogen or oxygen atom wherein the heterocylic grouphas optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl),

R¹¹ is hydrogen atom or a lower alkyl,

R¹² is a cycloalkyl, or a phenyl which has optionally 1 to 3substituents selected from a lower alkoxy, a lower alkyl and a halogenatom,

W is a group of the formula: --(CH₂)_(p) -- (p is an integer of 3 to 5),or a group of the formula: --CH═CH--(CH₂)_(q) -- (q is an integer of 1to 3), the carbon atom of these groups: --(CH₂)_(p) -- and--CH═CH--(CH₂)_(q) -- being optionally replaced by oxygen atom, sulfuratom, sulfinyl, sulfonyl, or a group of the formula: ##STR10## ishydrogen atom, a cycloalkyl, or a lower alkyl), and further said--(CH₂)_(p) -- and --CH═CH--(CH₂)_(q) -- groups having optionally 1 to 3substituents selected from a lower alkyl having optionally a hydroxysubstituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a loweralkanoyloxy having optionally a halogen substituent, an amino-loweralkyl having optionally a substituent selected from a lower alkyl and alower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a loweralkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of theformula: ##STR11## an aminocarbonyloxy having optionally a lower alkylsubstituent, a lower alkoxy, a lower alkoxycarbonyl-substituted loweralkoxy, a carboxy-substituted lower alkoxy, an aminocarbonyl-loweralkoxy having optionally a lower alkyl substituent, an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, alower alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido,sulfoxyimino, a group of the formula: ##STR12## (R⁸¹ is hydrogen atom ora lower alkyl), hydrazino, pyrrolyl, an amino-lower alkanoyloxy havingoptionally a lower alkyl substituent, a group of the formula: ##STR13##(A is as defined above, and R⁸² and R⁸³ are the same or different andare each hydrogen atom, a lower alkyl, a carbamoyl-substituted loweralkyl, a hydroxy-substituted lower alkyl, or a pyridyl-lower alkyl, orR⁸² and R⁸³ may bind together with nitrogen atom to which they bond toform a 5- or 6-membered saturated heterocyclic group with or withoutbeing intervened with nitrogen, oxygen or sulfur atom wherein theheterocyclic group has optionally a substituent selected from oxo, alower alkyl, a lower alkanoyl, and carbamoyl), and a group of theformula: ##STR14## (wherein n is as defined above, and R¹⁴ and R¹⁵ arethe same or different and are each hydrogen atom, a lower alkyl, a loweralkenyl, a lower alkanoyl, a cycloalkyl, an oxiranyl-substituted loweralkyl, a lower alkyl having optionally 1 to 2 substituents selected froma lower alkoxy, hydroxy and an amino having optionally a lower alkylsubstituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, a loweralkylsulfonyl, benzoyl, a lower alkoxy-carbonyl, anilinocarbonyl, anaminocarbonyl having optionally a lower alkyl substituent, acyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted loweralkyl, a carbamoyl-substituted lower alkyl, a carboxy-substituted loweralkyl, a tetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted lower alkanoyl, an imidazolyl-substituted loweralkanoyl, an amino-lower alkanoyl having optionally a substituentselected from a lower alkyl and a lower alkoxycarbonyl, anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ may bind together withnitrogen atom to which they bond to form a 5- or 6-membered saturatedheterocyclic group with or without being intervened with nitrogen oroxygen, wherein the heterocyclic group may optionally have a substituentselected from a lower alkyl, a phenyl-lower alkyl or a lower alkanoyl).

The benzoheterocyclic compounds of the formula (1) and their salts haveexcellent vasopressin antagonistic activities and vasodilating activity,hypotensive activity, activity for inhibiting saccharide release inliver, activity for inhibiting growth of mesangium cells, water diureticactivity, platelet agglutination inhibitory activity and are useful asvasodilator, hypotensive agent, water diuretics, platelet agglutinationinhibitor and are used for the prophylaxis and treatment ofhypertension, edema, ascites, heart failure, renal function disorder,vasopressin parasecretion syndrome (SIADH), hepatocirrhosis,hyponatremia, hypokaliemia, diabetic, circulation disorder, and thelike.

Each group in the above formula (1) includes specifically the followinggroups.

The "lower alkoxy" includes a straight chain or branched chain alkoxygroup having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy,isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, and the like.

The "lower alkyl" includes a straight chain or branched chain alkylgroup having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl,isopropyl, butyl, tert-butyl, pentyl, hexyl, and the like.

The "halogen atom" includes fluorine atom, chlorine atom, bromine atomand iodine atome.

The "amino having optionally a lower alkyl substituent" includes anamino having optionally one or two substituents selected from a straightchain or branched chain alkyl group having 1 to 6 carbon atoms, forexample, amino, methylamino, ethylamino, propylamino, isopropylamino,butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino,diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino,N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino,N-methyl-N-hexylamino, and the like.

The "lower alkenyl" includes a straight chain or branched chain alkenylgroup having 2 to 6 carbon atoms, for example, vinyl, allyl, 2-butenyl,3-butenyl, 1-methylallyl, 2-pentenyl, 2-hexenyl, and the like.

The "lower alkyl which has optionally a substituent selected from ahalogen atom and hydroxy" includes a straight chain or branched chainalkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3substituents selected from a halogen atom and hydroxy, for example, inaddition to the above-mentioned lower alkyl groups, hydroxymethyl,2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihyroxypropyl,4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl,5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl,2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl,chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl,dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl,2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl,4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl,3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, and the like.

The "lower alkylene" includes a straight chain or branched chainalkylene group having 1 to 6 carbon atoms, for example, methylene,ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene,1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene,pentamethylene, hexamethylene, and the like.

The "lower alkanoyloxy" includes a straight chain or branched chainalkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy,acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy,tert-butylcarbonyloxy, hexanoyloxy, and the like.

The "lower alkylthio" includes a straight chain or branched chainalkylthio group having 1 to 6 carbon atoms, for example, methylthio,ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio,pentylthio, hexylthio, and the like.

The "lower alkanoyl" includes a straight chain or branched chainalkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl,propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl,hexanolyl, and the like.

The "lower alkoxycarbonyl" includes a straight chain or branched chainalkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety,for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl,pentyloxycarbonyl, hexyloxycarbonyl, and the like.

The "amino having optionally a substituent selected from a lower alkyland a lower alkanoyl" includes an amino having optionally one or twosubstituents selected from a straight chain or branched chain alkylgroup having 1 to 6 carbon atoms and a straight chain or branched chainalkanoyl group having 1 to 6 carbon atoms, for example, amino,methylamino, ethylamino, propylamino, isopropylamino, butylamino,tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino,dipropylamino, dibutylamino, dipentylamino, dihexylamino,N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino,N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino,N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino,N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino,N-ethyl-N-acetylamino, and the like.

The "cycloalkyl" includes a cycloalkyl having 3 to 8 carbon atoms, forexample, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, and the like.

The "lower alkanoyloxy-substituted lower alkoxy" includes a straightchain or branched chain alkoxy group having 1 to 6 carbon atoms which issubstituted by a straight chain or branched chain alkanoyloxy grouphaving 2 to 6 carbon atoms, for example, acetyloxymethoxy,2-propionyloxyethoxy, 1-butyryloxyethoxy, 3-acetyloxypropoxy,4-acetyloxybutoxy, 4-isobutyryloxybutoxy, 5-pentanoyloxypentyloxy,6-acetyloxyhexyloxy, 6-tert-butylcarbonyloxyhexyloxy,1,1-dimethyl-2-hexanoyloxyethoxy, 2-methyl-3-acetyloxypropoxy, and thelike.

The "carbamoyl-substituted lower alkoxy" includes acarbamoyl-substituted alkoxy group wherein the alkoxy moiety is astraight chain or branched chain alkoxy group having 1 to 6 carbonatoms, for example, carbamoylmethoxy, 2-carbamoylethoxy,1-carbamoylethoxy, 3-carbamoylpropoxy, 4-carbamoylbutoxy,5-carbamoylpentyloxy, 6-carbamoylhexyloxy,1,1-dimethyl-2-carbamoylethoxy, 2-methyl-3-carbamoylpropoxy, and thelike.

The "hydroxy-substituted lower alkoxy" includes a straight chain orbranched chain alkoxy group having 1 to 6 carbon atoms and having 1 to 3hydroxy substitutents, for example, hydroxymethoxy, 2-hydroxyethoxy,1-hydroxyethoxy, 3-hydroxypropoxy, 2,3-dihydroxypropoxy,4-hydroxybutoxy, 3,4-dihydroxybutoxy, 1,1-dimethyl-2-hydroxyethoxy,5-hydroxypentyloxy, 6-hydroxyhexyloxy, 2-metnyl-3-hydroxypropoxy,2,3,4-trihydroxybutoxy, and the like.

The "lower alkoxycarbonyl-substituted lower alkoxy" includes analkoxycarbonyl-substituted straight chain or branched chain alkoxy grouphaving 1 to 6 carbon atoms wherein the alkoxycarbonyl moiety is astraight chain or branched chain alkoxycarbonyl group having 1 to 6carbon atoms, for example, methoxycarbonylmethoxy,3-methoxycarbonylpropoxy, ethoxycarboxymethoxy, 3-ethoxycarbonylpropoxy,4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxY,6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy,2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy,hexyloxycarbonylmethoxy, and the like.

The "carboxy-substituted lower alkoxy" includes a carboxy-substitutedalkoxy group wherein the alkoxy moiety is a straight chain or branchedchain alkoxy group having 1 to 6 carbon atoms, for example,carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy,4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy,1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.

The "phthalimido-substituted lower alkoxy" includes a straight chain orbranched chain alkoxy group having 1 to 6 carbon atoms which issubstituted by phthalimido group, for example, phthalimidomethoxy,2-phthalimidoethoxy, 1-phthalimidoethoxy, 3-phthalimidopropoxy,4-phthalimidobutoxy, 5-phthalimidopentyloxy, 6-phthalimidohexyloxy,1,1-dimethyl-2-phthalimidoethoxy, 2-methyl-3-phthalimidopropoxy, and thelike.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R⁶ and R⁷ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen or oxygen atom"includes, for example, pyrrolidinyl, piperidinyl, piperazinyl,morpholino, and the like.

The "heterocyclic group having a substituent selected from piperidinyland a lower alkyl" includes a heterocyclic group having 1 to 3substituents selected from piperidinyl and a straight chain or branchedchain alkyl group having 1 to 6 carbon atoms, for example,4-methyxpiperiazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl,2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl,3-pentylmorpholino, 4-hexylpiperazinyl, 4-(1-piperidinyl)piperidinyl,3-(1-piperidinyl)pyrrolidinyl, 3-(1-piperidinyl)-4-methylpiperazinyl,3-(1-piperidinyl)morpholino, and the like.

The "phenyl(lower)alkanoyl" includes a phenylalkanoyl wherein thealkanoyl moiety is a straight chain or branched chain alkanoyl grouphaving 2 to 6 carbon atoms, for example, phenylacetyl,3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl,2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, andthe like.

The "cycloalkyl-lower alkanoyl" includes C₃ -C₈ cycloalkyl-alkanoylgroup wherein the alkanoyl moiety is a straight chain or branched chainalkanoyl having 2 to 6 carbon atoms, for example, cyclohexylacetyl,3-cyclopropylpropionyl, 2-cyclopentylpropionyl, 4-cyclohexylbutyryl,2,2-dimethyl-3-cycloheptylpropionyl, 5-cyclooctylpentanoyl,6-cyclohexylhexanoyl, and the like.

The "cycloalkylcarbonyl" includes a cycloalkylcarbonyl having 3 to 8carbon atoms, for example, cyclopropylcarbonyl, cyclobutylcarbonyl,cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl,cyclooctylcarbonyl, and the like.

The "amino having optionally a lower alkanoyl substituent" includes anamino having optionally a straight chain or branched chain alkanoylgroup having 1 to 6 carbon atoms, for example, amino, formylamino,acetylamino, propionylamino, butyrylamino, isobutyrylamino,pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.

The "phenoxy-lower alkanoyl which phenyl ring has optionally 1 to 3substituents selected from a lower alkyl, a lower alkoxy and an aminohaving optonally a lower alkanoyl substituent" includes aphenoxyalkanoyl group wherein the alkanoyl moiety is a straight chain orbranched chain alkanoyl having 2 to 6 carbon atoms and the phenyl ringhas optionally 1 to 3 substituents selected from a straight chain orbranched chain alkyl having 1 to 6 carbon atoms, a straight chain orbranched chain alkoxy having 1 to 6 carbon atoms and an amino havingoptionally a straight chain or branched chain alkanoyl having 1 to 6carbon atoms, for example, phenoxyacetyl, 3-phenoxypropionyl,2-phenoxypropionyl, 4-phenoxybutyryl, 2,2-dimethyl-3-phenoxypropionyl,5-phenoxypentanoyl, 6-phenoxyhexanoyl, (2-aminophenoxy)acetyl,3-(4-aminophenoxy)propionyl, (2-methylphenoxy)acetyl,(4-methylphenoxy)acetyl, (3-methylphenoxy)acetyl,(3-methoxyphenoxy)acetyl, (3-acetylaminophenoxy)acetyl,4-(2-propionylaminophenoxy)butyryl,2,2-dimethyl-3-(4-butyrylaminophenoxy)propionyl,5-(2-pentanoylaminophenoxy)pentanoyl,6-(4-hexanoylaminophenoxy)hexanoyl, 3-(2-ethylphenoxy)propionyl,2-(4-propylphenoxy)propionyl, 4-(4-butylphenoxy)butyryl,5-(3-pentylphenoxy)pentanoyl, 6-(4-hexylphenoxy)hexanoyl,(2,3-dimethylphenoxy)acetyl, (2,5-dimethylphenoxy)acetyl,(3,4-dimethylphenoxy)acetyl, (3,4,5-trimethylphenoxy)acetyl,3-(4-ethoxyphenoxy)propionyl, 2-(2-propoxyphenoxy)propionyl,4-(3-butoxyphenoxy)butyryl, 5-(4-pentyloxyphenoxy)pentanoyl,6-(4-hexyloxyphenoxy)hexanoyl, (3,4-dimethoxyphenoxy)acetyl,(3,5-dimethoxyphenoxy)acetyl, (2,4-dimethoxyphenoxy)acetyl,(3,4,5-trimethoxyphenoxy)acetyl, (2-acetylamino-4-methylphenoxy)acetyl,(4-acetylamino-3-methoxyphenoxy)acetyl, and the like.

The "phthalimido-substituted lower alkanoyl" includes a straight chainor branched chain alkanoyl group having 2 to 6 carbon atoms which issubstituted by phthalimido group, for example, 2-phthalimidoacetyl,3-phthalimidopropionyl, 2-phthalimidopropionyl, 4-phthalimidobutyryl,2,2-dimethyl-3-phthalimidopropionyl, 5-phthalimidopentanoyl,6-phthalimidohexanoyl, 3-methyl-4-phthalimidobutyryl, and the like.

The "lower alkoxycarbonyl-lower alkanoyl" includes analkoxycarbonyl-alkanoyl group wherein the alkoxy moiety is a straightchain or branched chain alkoxy having 1 to 6 carbon atoms and thealkanoyl moiety is a straight chain or branched chain alkanoyl having 2to 6 carbon atoms, for example, methoxycarbonylacetyl,3-methoxycarbonylpropionyl, ethoxycarbonylacetyl,3-ethoxycarbonylpropionyl, 4-ethoxycarbonylbutyryl,3-propoxycarbonylpropionyl, 2-methoxycarbonylpropionyl,6-propoxycarbonylhexanoyl, 5-isopropoxycarbonylpentanoyl,2,2-dimethyl-3-butoxycarbonylpropionyl,2-methyl-3-tert-butoxycarbonylpropionyl, pentyloxycarbonylacetyl,hexyloxycarbonylacetyl, and the like.

The "carboxy-lower alkanoyl" includes a carboxyalkanoyl group whereinthe alkanoyl moiety is a straight chain or branched chain alkanoylhaving 2 to 6 carbon atoms, for example, carboxyacetyl,3-carboxypropionyl, 2-carboxypropionyl, 4-carboxybutyryl,2,2-dimethyl-3-carboxypropionyl, 5-carboxypentanoyl, 6-carboxyhexanoyl,and the like.

The "naphthyloxy-lower alkanoyl" includes a naphthyloxy-alkanoyl groupwherein the alkanoyl moiety is a straight chain or branched chainalkanoyl having 2 to 6 carbon atoms, for example, naphtyloxyacetyl,3-naphtyloxypropionyl, 2-naphtyloxypropionyl, 4-naphthyloxybutyryl,2,2-dimethyl-3-naphthyloxypropionyl, 5-naphthyloxypentanoyl,6-naphthyloxyhexanoyl, and the like.

The "phenyl-lower alkoxycarbonyl" includes a phenylalkoxycarbonylwherein the alkoxycarbonyl moiety is a straight chain or branched chainalkoxycarbonyl group having 1 to 6 carbon atoms, for example,benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl,3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl,5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl,1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl,and the like.

The "lower alkyl having optionally a hydroxy substituent" includes astraight chain or branched chain alkyl having 1 to 6 carbon atoms andhaving optionally 1 to 3 hydroxy substituents, for example,hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl,2,3-dihydroxyethyl, 4-hydroxybutyl, 3,4-dihydroxybutyl,1,1-dimethyl-2-hydroxyethyl, 5-hydroxypentyl, 6-hydroxyhexyl,2-methyl-3-hydroxypropyl, 2,3,4-trihydroxybutyl, and the like.

The "phenyl-lower alkyl" includes a phenylalkyl group wherein the alkylmoiety is a straight chain or branched chain alkyl group having 1 to 6carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl,3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl,1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, and the like.

The "phenoxy-lower alkyl" includes a phenoxyalkyl group wherein thealkyl moiety is a straight chain or branched chain alkyl group having 1to 6 carbon atoms, for example, phenoxymethyl, 1-phenoxyethyl,2-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 5-phenoxypentyl,6-phenoxyhexyl, 1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl,and the like.

The "phenyl which has optionally 1 to 3 substituents selected from alower alkyl, a lower alkoxy and a halogen atom" includes a phenyl groupwhich has optionally 1 to 3 substituents selected from a straight chainor branched chain alkyl group having 1 to 6 carbon atoms, a straightchain or branched chain alkoxy group having 1 to 6 carbon atoms and ahalogen atom, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl,4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl,4-isopropoxyphenyl, 4-pentyloxyphenyl, 2,4-dimethoxyphenyl,4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3-ethoxy-4-methoxyphenyl,2,3-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,5-dimethoxyphenyl,2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dipentyloxyphenyl,3,4,5-trimethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl,3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl,3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl,2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-difluorophenyl,3,5-dibromophenyl, 3,4,5-trichlorophenyl, 2-methoxy-3-chlorophenyl,2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl,3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl,4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl,2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl,3,4,5-trimethylphenyl, 3-chloro-4-methylphenyl,3-methoxy-4-methyl-5-iodophenyl, 3,4-dimethoxy-5-bromophenyl,3,5-diiodo-4-methoxyphenyl, and the like.

The "amino-lower alkyl having optionally a lower alkyl substituent"includes a straight chain or branched chain alkyl group having 1 to 6carbon atoms which is substituted by an amino group having optionally 1to 2 substituents of a straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl,1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl,1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl,4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl,dimethylaminomethyl, (N-ethyl-N-propylamino)methyl,2-(N-methyl-N-hexylamino)ethyl, and the like.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R⁹ and R¹⁰ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen or oxygen atom"includes, for example, pyrrolidinyl, piperidinyl, piperazinyl,morpholino, and the like.

The "heterocyclic group having a substituent selected from a loweralkyl, a lower alkoxycarbonyl and piperidinyl" includes a heterocyclicgroup having 1 to 3 substituents selected from a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, a straight chainor branched chain alkoxycarbonyl having 1 to 6 carbon atoms andpiperidinyl, for example, in addition to the above-mentionedheterocyclic groups having a substituent of a lower alkyl andpiperidinyl, 4-methoxycarbonylpiperazinyl, 4-ethoxycarbonylpiperidinyl,3-propoxycarbonylpyrrolidinyl, 2-pentyloxycarbonylmorpholino,4-hexyloxycarbonylpiperidinyl, 4-ethoxycarbonyl-3-methylpiperidinyl,3-methyl-4-ethoxycarbonylpiperazinyl, and the like.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R¹⁴ and R¹⁵ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen or oxygen atom"includes, for example, pyrrolidinyl, piperidinyl, piperazinyl,morpholino, and the like.

The "heterocyclic group having a lower alkyl substituent" includes aheterocyclic group having 1 to 3 substituents of a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, for example,4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl,2-propylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl,3-pentylmorpholino, 4-hexylpiperazinyl, and the like.

The heterocyclic ring in the formula (1) includes tetrahydroquinolyl,2,3,4,5-tetrahydro-1H-benzazepinyl, 1,2,3,4,5,6-hexahydrobenzazocinyl,1,2-dihydroquinolyl, 2,3-dihydro-1H-benzazepinyl,1,2,3,4-tetrahydrobenzazocinyl, and the like.

The heterocyclic ring in the formula (1) wherein the carbon atom in thegroup of the formula: --(CH₂)_(p) -- or --CH═CH--(CH₂)_(q) -- for W isreplaced by oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a group ofthe formula: ##STR15## (R¹³ is hydrogen atom or a lower alkyl) includesa heterocylic group wherein the carbon atom in the group of the formula:--(CH₂)_(p) -- or --CH═CH--(CH₂)_(q) -- for W is replaced by oxygenatom, sulfur atom, sulfinyl, sulfonyl, or a group of the formula:##STR16## (R¹³ is hydrogen atom or a straight chain or branched chainalkyl having 1 to 6 carbon atoms ), for example,3,4-dihydro-2H-1,4-benzoxazinyl, 1,2,3,5-tetrahydro-4,1-benzoxazepinyl,1,2,3,4-tetrahydroquinoxalinyl,1,2,3,4,5,6-hexahydro-1,5-benzodiazocinyl,5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocinyl, 4-methyl-I,2,3,4-tetrahydroquinoxalinyl, 1,2,3,4-tetrahydro-5,1-benzoxazepinyl,3,4-dihydro-2H,-1,4-benzothiazinyl,2,3,4,5-tetrahydro-1,5-benzothiazepinyl,1,2,3,5-tetrahydro-4,1-benzothiazepinyl, 4-ethyl-i,2,3,4-tetrahydroquinoxalinyl, 4-propyl-1,2,3,4-tetrahydroquinoxalinyl,4-butyl-1,2,3,4-tetrahydroquinoxalinyl,4-pentyl-1,2,3,4-tetrahydroquinoxalinyl,4-hexyl-1,2,3,4-tetrahydroquinoxalinyl,2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-propyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-butyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-pentyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,4-hexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinyl,2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-ethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-propyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,-butyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-pentyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,5-hexyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepinyl,3,4-dihydro-1-oxo-2H-1,4-benzothiazepinyl,3,4-dihydro-1,1-dioxo-2H-1,4-benzothiazepinyl,1-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepinyl,1,1-dioxo-2,3,4,5-tetrahydro-1,5-benzothiazepinyl,4-oxo-1,2,3,5-tetrahydro-4,1-benzothiazepinyl,4,4-dioxo-1,2,3,5-tetrahydro-4,1-benzothiazepinyl, and the like.

The "halogen-substituted lower alkoxy" includes a straight chain orbranched chain alkoxy group having 1 to 6 carbon atoms which has 1 to 3substituents of a halogen atom, for example, trifluoromethoxy,trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy,iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy,2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy,2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy,5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy,5,6-dichlorohexyloxy, and the like.

The "halogen-substituted lower alkanoyl" includes a straight chain orbranched chain alkanoyl group having 1 to 6 carbon atoms which has 1 to3 substituents of a halogen atom, for example, 2,2,2-trifluoroacetyl,2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl,2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl,3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl,2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl,5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl,5,6-dibromohexanoyl, and the like.

The "aminocarbonyl-lower alkoxy having a lower alkyl substituent"includes a straight chain or branched chain alkoxy group having 1 to 6carbon atoms which is substituted by an aminocarbonyl group having 1 to2 substituents of a straight chain or branched chain alkyl group having1 to 6 carbon atoms, for example, methylaminocarbonylmethoxy,1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy,3-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy,5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy,dimethylaminocarbonylmethoxy, 3-diethylaminocarbonylpropoxy,diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino)carbonylmethoxy,2-(N-methyl-N-hexylamino)carbonylethoxy, and the like.

The "carbamoyl-lower alkyl" includes a carbamoyl-substituted alkyl groupwherein the alkyl moiety is a straight chain or branched chain alkylgroup having 1 to 6 carbon atoms, for example, carbamoylmethyl,2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl,5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl,2-methyl-3-carbamoylpropyl, and the like.

The "amino-lower alkanoyl having optionally a lower alkyl substituent"includes a straight chain or branched chain alkanoyl having 2 to 6carbon atoms which is substituted by an amino group having optionally 1to 2 substituents of a straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms, for example, 2-aminoacetyl,3-aminopropionyl, 2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl,6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl,2-methyl-3-aminopropionyl, 2-methylaminoacetyl, 2-ethylaminopropionyl,3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl,5-pentylaminopentanoyl, 6-hexylaminohexanoyl, 2-dimethylaminoacetyl,2-diethylaminoacetyl, 2-(N-ethyl-N-propylamino)acetyl,3-(N-methyl-N-hexylamino)propionyl, and the like.

The "amino-lower alkyl having optionally a lower alkanoyl substituent"includes a straight chain or branched chain alkyl having 1 to 6 carbonatoms which is substituted by an amino group having optionally asubstituent of a straight chain or branched chain alkanoyl group having1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl,1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl,1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl,4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl,formylaminomethyl, and the like.

The "anilinocarbonyl having optionally a lower alkyl substituent on thephenyl ring" includes an anilinocarbonyl group having optionally 1 to 3substituents of a straight chain or branched chain alkyl group having 1to 6 carbon atoms on the phenyl ring, for example, anilinocarbonyl,2-methylanilinocarbonyl, 3-methylanilinocarbonyl,4-methylanilinocarbonyl, 2-ethylanilinocarbonyl, 3-ethylanilinocarbonyl,4-ethylanilinocarbonyl, 4-isopropylanilinocarbonyl,3-butylanilinocarbonyl, 4-pentylanilinocarbonyl, 4-hexylanilinocarbonyl,3,4-dimethylanilinocarbonyl, 3,4-diethylanilinocarbonyl,2,4-dimethylanilinocarbonyl, 2,5-dimethylanilinocarbonyl,2,6-dimethylanilinocarbonyl, 3,4,5-trimethylanilinocarbonyl, and thelike.

The "phenylsulfonyl which has optionally a substituent selected from ahalogen and a lower alkyl on the phenyl ring" includes a phenylsulfonylgroup which has optionally 1 to 3 substitutents selected from a straightchain or branched chain alkyl group having 1 to 6 carbon atoms and ahalogen atom, for example, phenylsulfonyl, 2-chlorophenylsulfonyl,3-chlorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-fluorophenylsulfonyl,3-fluorophenylsulfonyl, 4-fluorophenylsulfonyl, 2-bromophenylsulfonyl,3-bromophenylsulfonyl, 4-bromophenylsulfonyl, 2-iodophenylsulfonyl,3-iodophenylsulfonyl, 4-iodophenylsulfonyl, 3,4-dichlorophenylsulfonyl,3,5-dichlorophenylsulfonyl, 2,6-dichlorophenylsulfonyl,2,3-dichlorophenylsulfonyl, 2,4-dichlorophenylsulfonyl,3,4-difluorophenylsUlfonyl, 3,5-dibromophenylsulfonyl,3,4,5-trichlorophenylsulfonyl, 2-ethyl-3-chlorophenylsulfonyl,2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl,2-ethylphenylsulfonyl, 3-ethylphenylsulfonyl, 4-ethylphenylsulfonyl,4-isopropylphenylsulfonyl, 3-butylphenylsulfonyl,4-pentylphenylsulfonyl, 4-hexylphenylsulfonyl,3,4-dimethylphenylsulfonyl, 3,4-diethylphenylsulfonyl,2,4-dimethylphenylsulfonyl, 2,5-dimethylphenylsulfonyl,2,6-dimethylphenylsulfonyl, 3,4,6-trimethylphenylsulfonyl,3,4,5-trimethylphenylsulfonyl, 3-chloro-4-methylphenylsulfonyl,4-methyl-5-iodophenylsulfonyl, 3,4-dimethyl-5-bromophenylsulfonyl,3,5-diiodo-4-methylphenylsulfonyl, and the like.

The "phthalimido-substituted lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by phthalimido group, for example, phthalimidomethyl,2-phthalimidoethyl, 1-phthalimidoethyl, 3-phthalimidopropyl,4-phthalimidobutyl, 5-phthalimidopentyl, 6-phthalimidohexyl,1,1-dimethyl-2-phthalimidoethyl, 2-methyl-3-phthalimidopropyl, and thelike.

The "lower alkynyl" includes a straight chain or branched chain alkynylhaving 2 to 6 carbon atoms, for example, ethynyl, 2-propynyl, 2-butynyl,3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 2-hexynyl, and the like.

The "benzoyl which has optionally a halogen substituent on the phenylring" includes a benzoyl group which has optionally 1 to 3 substithentsof a halogen atom on the phenyl ring, for example, benzoyl,2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl,3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 3-bromobenzoyl,4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzoyl,3,4-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,6-dichlorobenzoyl,2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4-difluorobenzoyl,3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, and the like.

The "phenyl-lower alkoxy" includes a phenylalkoxy group wherein thealkoxy moiety is a straight chain or branched chain alkoxy group having1 to 6 carbon atoms, for example, benzyloxy, 2-phenylethoxy,1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy,6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3-phenylpropoxy,and the like.

The "amino-lower alkoxy having optionally a substituent selected from alower alkyl and a lower alkanoyl" include a straight chain.or branchedchain alkoxy group having 1 to 6 carbon atoms which is substituted by anamino group having optionally 1 to 2 substituents selected from astraight chain or branched chain alkyl group having 1 to 6 carbon atomsand a straight chain or branched chain alkanoyl group having 1 to 6carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy,3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy,1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy,1-acetylaminoethoxy, 2-propionylaminoethoxy, 3-isopropionylaminopropoxy,4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy,6-hexanoylaminohexyloxy, formylaminomethoxy, methylaminomethoxy,1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy,4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy,dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy,2-(N-methyl-N-hexylamino)ethoxy, and the like.

The "benzoyloxy which has optionally a halogen substituent on the phenylring" includes a benzoyloxy group which has optionally 1 to 3substituents of a halogen atom on the phenyl ring, for example,benzoyloxy, 2-chlorobenzoyloxy, 3-chlorobenzoyloxy, 4-chlorobenzoyloxy,2-fluorobenzoyloxy, 3-fluorobenzoyloxy, 4-fluorobenzoyloxy,2-bromobenzoyloxy, 3-bromobenzoyloxy, 4-bromobenzoyloxy,2-iodobenzoyloxy, 3-iodobenzoyloxy, 4-iodobenzoyloxy,3,4-dichlorobenzoyloxy, 3,5-dichlorobenzoyloxy, 2,6-dichlorobenzoyloxy,2,3-dichlorobenzoyloxy, 2,4-dichlorobenzoyloxy, 3,4-difluorobenzoyloxy,3,5-dibromobenzoyloxy, 3,4,5-trichlorobenzoyloxy, and the like.

The "lower alkanoyloxy-substituted lower alkyl" includes a straightchain or branched chain alkyl group having 1 to 6 carbon atoms which issubstituted by a straight chain or branched chain alkanoyloxy grouphaving 2 to 6 carbon atoms, for example, acetyloxymethyl,2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl,4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl,6-acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl,1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and thelike.

The "lower alkylsulfonyloxy-lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by a straight chain or branched chain alkylsulfonyloxy grouphaving 1 to 6 carbon atoms, for example, methylsulfonyloxymethyl,1-ethylsulfonyloxyethyl, 2-propylsulfonyloxyethyl,3-isopropylsulfonyloxypropyl, 4-hutylsulfonyloxybutyl,5-pentylsulfoyloxypentyl, 6-hexylsulfonyloxyhexyl,1,1-dimethyl-2-methylsulfoyloxyethyl, 2-methyl-3-ethylsulfonyloxypropyl,and the like.

The "azido-lower alkyl" includes a straight chain or branched chainalkyl group having 1 to 6 carbon atoms which is substituted by an azidogroup, for example, azidomethyl, 1-azidoethyl, 2-azidoethyl,3-azidopropyl, 4-azidobutyl, 5-azidopentyl, 6-azidohexyl,1,1-dimethyl-2-azidoethyl, 2-methyl-3-azidopropyl, and the like.

The "lower alkanoyloxyimino" includes a straight chain or branched chainalkanoyloxyimino group having 1 to 6 carbon atoms, for example,formyloxyimino, acetyloxyimino, propionyloxyimino, butyryloxyimino,isobutyryloxyimino, pentanoyloxyimino, tert-butylcarbonyloxyimino,hexanoyloxyimino, and the like.

The "lower alkylidene" includes a straight chain or branched chainalkylidene group having 1 to 6 carbon atoms, for example, methylidene,ethylidene, propylidene, isopropylidene, butylidene, pentylidene,hexylidene, and the like.

The "oxiranyl-substituted lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by oxiranyl group, for example, oxiranylmethyl,1-oxiranylethyl, 2-oxiranylethyl, 3-oxiranylpropyl, 4-oxiranylbutyl,5-oxiranylpentyl, 6-oxiranylhexyl, 1,1-dimethyl-2-oxiranylethyl,2-methyl-3-oxiranylpropyl, and the like.

The "lower alkyl having 1 to 2 substituents selected from a loweralkoxy, hydroxy and an amino having optionally a lower alkylsubstituent" includes a straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms and having 1 to 2 substituents selected froma straight chain or branched chain alkoxy group having 1 to 6 carbonatoms, hydroxy and an amino having optionally a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, for example,methoxymethyl, 1-ethoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl,4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl,1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl,3-methoxy-2-hydroxypropyl, hydroxymethyl, 2-hydroxyethyl,1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxyethyl, 4-hydroxybutyl,3,4-dihydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,6-dihydroxyhexyl,5-hydroxypentyl, 6-hydroxyhexyl,6-(N-ethyl-N-methylamino)-5-methoxyhexyl, 2-methyl-3-hydroxypropyl,aminomethyl, 1-aminoethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl,5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl,2-methyl-3-aminopropyl, methylaminomethyl, ethylaminomethy,propylaminomethyl, isopropylaminomethyl, butylaminomethyl,tert-butylaminomethyl, pentylaminomethyl, hexylaminomethyl,dimethylaminomethyl, diethylaminomethyl, dipropylaminomethyl,dibutylaminomethyl, dipentylaminomethyl, dihexylaminomethyl,N-methyl-N-ethylaminomethyl, N-methyl-N-propylaminomethyl,N-methyl-N-butylaminomethyl, N-methyl-N-hexylaminomethyl,1-methylaminoethyl, 2-ethylaminoethyl, 3-propylaminopropyl,4-butylaminobutyl, 1,1-dimethyl-2-pentylaminoethyl, 5-hexylaminopentyl,6-dimethylaminohexyl, 4-dimethylaminobutyl, 2-diethylaminoethyl,1-(N-methyl-N-hexylamino)ethyl, 3-dihexylaminopropyl,6-diethylaminohexyl, 4-dibutylaminobutyl,2-(N-methyl-N-pentylamino)ethyl, 2-hydroxy-3-diethylaminopropyl,3-hydroxy-4-methylaminobutyl, 5-hydroxy-6-diethylaminohexyl,4-hydroxy-5-dimethylaminopentyl, 4-hydroxy-5-methylaminopentyl,4-hydroxy-5-diethylaminopentyl, 5-hydroxy-6-ethylaminohexyl,5-hydroxy-6-isopropylaminohexyl, 5-hydroxy-6-aminohexyl, and the like.

The "aminocarbonyloxy having optionally a lower alkyl substituent"includes an aminocarbonyloxy group having optionally 1 to 2 substituentsof a straight chain or branched chain alkyl group having 1 to 6 carbonatoms, for example, aminocarbonyloxy, methylaminocarbonyloxy,ethylaminocarbonyloxy, propylaminocarbonyloxy,isopropylaminocarbonyloxy, butylaminocarbonyloxy,tert-butylaminocarbonyloxy, pentylaminocarbonyloxy,hexylaminocarbonyloxy, dimethylaminocarbonyloxy,diethylaminocarbonyloxy, dipropylaminocarbonyloxy,dibutylaminocarbonyloxy, dipentylaminocarbonyloxy,dihexylaminocarbonyloxy, N-methyl-N-ethylaminocarbonyloxy,N-ethyl-N-propylaminocarbonyloxy, N-methyl-N-butylaminocarbonyloxy,N-methyl-N-hexylaminocarbonyloxy, and the like.

The "lower alkanoyloxy having optionally a halogen substituent" includesa straight chain or branched chain alkanoyloxy group having 1 to 6carbon atoms which has optionally 1 to 3 substituents of a halogen atom,for example, in addition to the above lower alkanoyl group,2,2,2-trifluoroacetyloxy, 2,2,2-trichloroacetyloxy, 2-chloroacetyloxy,2-bromoacetyloxy, 2-fluoroacetyloxy, 2-iodoacetyloxy,2,2-difluoroacetyloxy, 2,2-dibromoacetyloxy,3,3,3-trifluoropropionyloxy, 3,3,3-trichloropropionyloxy,3-chloropropionyloxy, 2,3-dichloropropionyloxy,4,4,4-trichlorobutyryloxy, 4-fluorobutyryloxy, 5-chloropentanoyloxy,3-chloro-2-methylpropionyloxy, 6-bromohexanoyloxy,5,6-dibromohexanoyloxy, and the like.

The "amino-lower alkyl having optionally a substituent selected from alower alkyl and a lower alkanoyl" include a straight chain or branchedchain alkyl group having 1 to 6 carbon atoms which is substituted by anamino group having optionally 1 to 2 substituents selected from astraight chain or branched chain alkyl group having 1 to 6 carbon atomsand a straight chain or branched chain alkanoyl group having 1 to 6carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl,3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl,1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, acetylaminomethyl,1-acetylaminoethyl, 2-propionylaminoethyl, 3-isopropionylaminopropyl,4-butyrylaminobutyl, 5-pentanoylaminopentyl, 6-hexanoylaminohexyl,formylaminomethyl, methylaminomethyl, 1-ethylaminoethyl,2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl,5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl,(N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, and thelike.

The "amino-lower alkanoyloxy having optionally a lower alkylsubstituent" includes a straight chain or branched chain alkanoyloxyhaving 2 to 6 carbon atoms which is substituted by an amino group havingoptionally 1 to 2 substituents of a straight chain or branched chainalkyl group having 1 to 6 carbon atoms, for example, 2-aminoacetyloxy,3-aminopropionyloxy, 2-aminopropionyloxy, 4-aminobutyrytoxy,5-aminopentanoyloxy, 6-aminohexanoyloxy,2,2-dimethyl-3-aminopropionyloxy, 2-methyl-3-aminopropionyloxy,2-methylaminoacetyloxy, 2-ethylaminopropionyloxy,3-propylaminopropionyloxy, 3-isopropylaminopropionyloxy,4-butylaminobutyryloxy, 5-pentylaminopentanoyloxy,6-hexylaminohexanoyloxy, 2-dimethylaminoacetyloxy,2-diethylaminoacetyloxy, 2-(N-ethyl-N-propylamino)acetyloxy,3-(N-methyl-N-hexylamino)propionyloxy, and the like.

The "pyridyl-lower alkyl" include a pyridylalkyl group wherein the alkylmoiety is a straight chain or branched chain alkyl group having 1 to 6carbon atoms, for example, (4-pyridyl)methyl, 1-(3-pyridyl)ethyl,2-(2-pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl,5-(4-pyridyl)pentyl, 6-(2-pyridyl)hexyl, 1,1-dimethyl-2-(3-pyridyl)ethyl, 2-methyl-3-(4-pyridyl)propyl, and the like.

The "5- or 6-membered saturated heterocyclic group which is formed bybinding the groups R⁸² and R⁸³ together with the nitrogen atom to whichthey bond with or without being intervened with nitrogen, oxygen orsulfur atom" includes, for example, pyrrolidinyl, piperidinyl,piperazinyl, morpholino, thiomorpholino, and the like.

The above heterocyclic group which has a substituent selected from oxo,a lower alkyl, a lower alkanoyl and carbamoyl includes the aboveheterocyclic groups which have 1 to 3 substituents selected from oxo, astraight chain or branched chain alkyl group having 1 to 6 carbon atoms,a straight chain or branched chain alkanoyl group having 1 to 6 carbonatoms, and carbamoyl group, for example, 4-methylpiperazinyl,3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl,3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino,4-hexylpiperazinyl, 2-methylthiomorpholino, 4-acetylpiperazinyl,2-propionylmorpholino, 3-butyrylthiomorpholino, 3-pentanoylpyrrolidinyl,4-hexanoylpiperidinyl, 3-methyl-4-acetylpiperazinyl,2-carbamoylpyrrolidinyl, 4-carbamoylpiperazinyl,3-carbamoylthiomorpholino, 2-carbamoylmorpholino,3-carbamoylpiperidinyl, 1-oxo-thiomorpholino, 1,1-dioxothiomorpholino,and the like.

The "lower alkylsulfonyl" includes a straight chain or branched chainalkylsulfonyl group having 1 to 6 carbon atoms, for example,methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl,butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, andthe like.

The "aminocarbonyl having optionally a lower alkyl substituent" includesan aminocarbonyl group having optionally 1 to 2 substituents of astraight chain or branched chain alkyl group having 1 to 6 carbon atoms,for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl,propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl,tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl,dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl,dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl,N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl,N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, and thelike.

The "cyano-substituted lower alkyl" includes a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms which issubstituted by cyano group, for example, cyanomethyl, 2-cyanoethyl,1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl,1,1-dimethyl-2-caynoethyl, 2-methyl-3-cyanopropyl, and the like.

The "lower alkoxycarbonyl-substituted lower alkyl" includes analkoxycarbonyl-substituted straight chain or branched chain alkyl grouphaving 1 to 6 carbon atoms wherein the alkoxycarbonyl moiety is astraight chain or branched chain alkoxycarbonyl group having 1 to 6carbon atoms, for example, methoxycarbonylmethyl,3-methoxycarbonylpropyl, ethoxycarboxymethyl, 3-ethoxycarbonylpropyl,4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl,6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl,2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl,hexyloxycarbonylmethyl, and the like.

The "carboxy-substituted lower alkyl" includes a carboxy-substitutedalkyl group wherein the alkyl moiety is a straight chain or branchedchain alkyl group having 1 to 6 carbon atoms, for example,carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl,4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl,1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxypropyl, and the like.

The "tetrahydropyranyloxy-substituted lower alkyl" includes atetrahydropyranyloxy-substituted straight chain or branched chain alkylgroup having 1 to 6 carbon atoms, for example,(2-tetrahydropyranyloxy)methyl, 2-(3-tetrahydropyranyloxy)ethyl,1-(4-tetrahydropyranyloxy)ethyl, 3-(2-tetrahydropyranyloxy)propyl,4-(3-tetrahydropyranyloxy)butyl, 5-(4-tetrahydropyranyloxy)pentyl,6-(2-tetrahydropyranyloxy)hexyl,1,1-dimethyl-2-(3-tetrahydropyranyloxy)ethyl,2-methyl-3-(4-tetrahydropyranyloxy)propyl, and the like.

The "piperidinyl having optionally a phenyl-lower alkyl substituent"includes a piperidinyl which has optionally a substituent of aphenylalkyl group wherein the alkyl moiety is a straight chain orbranched chain alkyl group having 1 to 6 carbon atoms, for example,piperidinyl, 1-benzyl-4-piperidinyl, 1-(2-phenylethyl)-3-piperidinyl,1-(1-phenylethyl)-2-piperidinyl, 1-(3-phenylpropyl)-4-piperidinyl,1-(4-phenylbutyl)-4-piperidinyl, 1-(5-phenylpentyl)-4-piperidinyl,1-(6-phenylhexyl)-4-piperidinyl,1-(1,1-dimethyl-2-phenylethyl)-3-piperidinyl,1-(2-methyl-3-phenylpropyl)-2-piperidinyl, and the like.

The "imidazolyl-substituted lower alkanoyl" includes animidazolyl-substituted alkanoyl group wherein the alkanoyl moiety is astraight chain or branched chain alkanoyl group having 2 to 6 carbonatoms, for example, (t-imidazolyl)acetyl, 3-(2-imidazolyl)propionyl,2-(4-imidazolyl)propionyl, 4-(1-imidazolyl)butyryl,2,2-dimethyl-3-(2-imidazolyl)propionyl, 5-(4-imidazolyl)pentanoyl,6-(1-imidazolyl)hexanoyl, and the like.

The "amino-lower alkanoyl having optionally a substituent selected froma lower alkyl and a lower alkoxycarbonyl" includes a straight chain orbranched chain alkanoyl having 2 to 6 carbon atoms which is substitutedby an amino group having optionally 1 to 2 substituents selected from astraight chain or branched chain alkyl group having 1 to 6 carbon atomsand a straight chain or branched chain alkoxycarbonyl group having 1 to6 carbon atoms, for example, 2-aminoacetyl, 3-aminopropionyl,2-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl,2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl,2-methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl,3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl,6-hexylaminohexanoyl, 2-dimethylaminoacetyl, 2-diethylaminoacetyl,2-(N-ethyl-N-propylamino)acetyl, 3-(N-methyl-N-hexylamino)propionyl,2-methoxycarbonylaminoacetyl, 2-ethoxycarbonylaminoacetyl,3-propoxycarbonylaminopropionyl, 4-butoxycarbonylaminobutyryl,2-tert-butoxycarbonylaminoacetyl, 5-pentyloxycarbonylaminopentanoyl,6-hexyloxycarbonylaminohexanoyl,2-(N-methyl-N-tert-butoxycarbonylamino)acetyl, and the like.

The "aminocarbonyl-lower alkyl having a lower alkyl substituent"includes a straight chain or branched chain alkyl group having 1 to 6carbon atoms which is substituted by an aminocarbonyl group having 1 to2 substituents of a straight chain or branched chain alkyl group having1 to 6 carbon atoms, for example, methylaminocarbonylmethyl,1-ethylaminocarbonylethyl, 2-propylaminocarbonylethyl,3-isopropylaminocarbonylpropyl, 4-butylaminocarbonylbutyl,5-pentylaminocarbonylpentyl, 6-hexylaminocarbonylhexyl,dimethylaminocarbonylmethyl, 3-diethylaminocarbonylpropyl,diethylaminocarbonylmethyl, (N-ethyl-N-propylamino)carbonylmethyl,2-(N-methyl-N-hexylamino)carbonylethyl, and the like.

The "amino-substituted lower alkoxy having optionally a lower alkylsubstituent" includes an amino-substituted straight chain or branchedchain alkoxy having 1 to 6 carbon atoms which has optionally 1 to 2substituents of a straight chain or branched chain alkyl having 1 to 6carbon atoms, such as aminomethoxy, 2-aminoethoxy, 1-aminoethoxy,3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy,1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy,1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy,4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy,dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy,2-(N-methyl-N-hexylamino)ethoxy, and the like.

The compounds of the present invention can be prepared by variousprocesses, for example, by the processes shown in the following reactionschemes. ##STR17## wherein R¹, R², R³, and W are the same as definedabove

The process of Reaction Scheme-1 is carried out by reacting abenzoheterocyclic compound of the formula (2) and a carboxylic acidcompound of the formula (3) by a conventional amido bond formingreaction. The amido bond forming reaction can be carried out under theconditions for the conventional amido bond forming reaction, forexample,

(a) a mixed acid anhydride process, i.e. a process of reacting thecarboxylic acid compound (3) with an alkyl-halocarboxylic acid to form amixed acid anhydride and reacting the resultant with the amine compound(2),

(b) an activated ester process, i.e. a process of converting thecarboxylic acid compound (3) into an activated ester, such asp-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazoleester, etc., and reacting the resultant with the amine compound (2),

(c) a carbodiimide process, i.e. a process of condensing the carboxylicacid compound (3) and the amine compound (2) in the presence of anactivating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole,etc.,

(d) other processes, i.e. a process of converting the carboxylic acidcompound (3) into a carboxylic anhydride by treatment with a dehydratingagent such as acetic anhydride, and reacting the resultant with theamine compound (2); a process of reacting an ester of the carboxylicacid compound (3) with a lower alcohol and the amine compound (2) at ahigh temperature under high pressure; a process of reacting an acidhalide compound of the carboxylic acid compound (3), i.e. a carboxylicacid halide, with the amine compound (2), and the like.

The mixed acid anhydride used in the above mixed acid anhydride process(a) is obtained by the known Schotten-Baumann reaction, and the reactionproduct is used without isolation from the reaction mixture for thereaction with the amine compound (2) to give the desired compound of theformula (1). The Schotten-Baumann reaction is usually carried out in thepresence of a basic compound. The basic compound is any conventionalcompounds used for the Schotten-Baumann reaction and includes, forexample, organic basic compounds such as triethylamine, trimethylamine,pyridine, dimethylaniline, N-methylmorpholine,1,5-diazabicyclo[4.3.0]nonene-5 (DBN),1,8-diazabicyclo[5.4.0]-undecene-7 (DBU), 1,4-diazabicyclo[2.2.21octane(DABCO), etc., and inorganic basic compounds such as potassiumcarbonate, sodium carbonate, potassium hydrogen carbonate, sodiumhydrogen carbonate, etc. The reaction is usually carried out at atemperature of from about -20° C. to about 100° C., preferably fromabout 0° C. to about 50° C., for about 5 minutes to about 10 hours,preferably about 5 minutes to about 2 hours.

The reaction of the thus obtained mixed acid anhydride with the aminecompound (2) is usually carried out at a temperature of from about -20°C. to about 150° C., preferably about 10° C. to about 50° C., for about5 minutes to about 10 hours, preferably about 5 minutes to about 5hours. The mixed acid anhydride process is usually carried out in anappropriate solvent. The solvent is any conventional solvents which areusually used in the mixed acid anhydride process and includes, forexample, halogenated hydrocarbons (e.g. chloroform, dichloromethanedichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, toluene,xylene, etc.), ethers (e.g. diethyl ether, diisopropyl ether,tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate,ethyl acetate, etc.), aprotic polar solvents (e.g.N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide,etc.), or a mixture of these solvents. The alkylhalocarboxylic acid usedin the mixed acid anhydride process includes, for example, methylchloroformate, methyl bromoformate, ethyl chloroformate, ethylbromoformate, isobutyl chloroformate, and the like. In said process, thecarboxylic acid compound (3), the alkylhalocarboxylic acid and the amine(2) are usually used in each equimolar amount, but preferably, thealkylhalocarboxylic acid and the carboxylic acid compound (3) are usedeach in an amount of about 1 to 1.5 mole to 1 mole of the amine (2).

Among the above other processes (d), in case of the process of reactingthe carboxylic acid halide with the amine compound (2), the reaction isusually carried out in the presence of a basic compound in anappropriate solvent. The basic compound is any conventional compoundsand includes, in addition to the basic compounds used for theabove-mentioned Schotten-Baumann reaction, sodium hydroxide, potassiumhydroxide, sodium hydride, potassium hydride. etc. The solvent includes,in addition to the solvents used for the above-mentioned mixed acidanhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol,3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.),acetonitrile, pyridine, acetone, water, and the like. The amount of theamine compound (2) and the carboxylic acid halide is not critical, butthe carboxylic acid halide is usually used at least in equimolar amount,preferably about 1 to 5 moles to 1 mole of the amine compound (2). Thereaction is usually carried out at a temperature of from about -20° C.to about 180° C., preferably from about 0° C. to about 150° C., forabout 5 minutes to about 30 hours.

The amido bond forming reaction in the above Reaction Scheme-1 may alsobe carried out by reacting the carboxylic acid compound (3) and theamine (2) in the presence of a condensation agent, i.e. phosphoriccompounds such as triphenylphosphine, diphenylphosphinyl chloride,phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate,diethyl phosphorocyanidate, diphenylphosphoric azide,bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc. The reaction isusually carried out in the presence of the solvent and basic compound asused in the above reaction of the carboxylic acid halide and the amine(2) at a temperature of from about -20° C. to about 150° C., preferablyabout 0° C. to about 100° C., for about 5 minutes to about 30 hours. Thecondensation agent and the carboxylic acid compound (3) are used atleast in equimolar amount, preferably about 1 to 2 moles, to 1 mole ofthe amine (2). ##STR18## wherein R¹, R², R⁴ and W are as defined above,R^(5a) is the same as R⁵ as defined above except excluding ananilinocarbonyl having optionally a lower alkyl substituent on thephenyl ring, a phenylsulfonyl having optionally a substituent selectedfrom a halogen-atom and a lower alkyl on the phenyl ring andquinolylsulfonyl.

The reaction of the compound (2b) and the compound (4) is carried out inthe same manner as in the reaction of the compound (2) and the compound(3) in the above Reaction Scheme-1. ##STR19## wherein R¹, R², R¹¹, R¹²and W are as defined above

The reaction of the compound (5) and the compound (6) is carried outunder the same conditions as used in the reaction of the compound (2)and the compound (3) in the above Reaction Scheme-1. ##STR20## whereinR¹, R², R⁵ and W are as defined above, and R^(4a) is a lower alkyl, R¹⁷and R¹⁸ are each hydrogen atom or a lower alkyl, and X is a halogenatom.

The reaction of the compound (7) and the compound (8) is usually carriedout in an inert solvent in the presence or absence of a basic compound.The inert solvent includes, for example, aromatic hydrocarbons (e.g.benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane,diethylene glycol dimethyl ether, etc.), halogenated hydrocarbons (e.g.dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols(e.g. methanol, ethanol, isopropanol, butanol, tert-butanol, etc.),acetic acid, ethyl acetate, acetone, acetonitrile, pyridine,dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide,etc., or a mixture of these solvents. The basic compound includes, forexample, carbonates (e.g. sodium carbonate, potassium carbonate, sodiumhydrogen carbonate, potassium hydrogen carbonate, etc.), metalhydroxides (e.g. sodium hydroxide, potassium hydroxide, etc.), sodiumhydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodiummethoxide, sodium ethoxide, etc.), and organic basic compounds (e.g.pyridine, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine,1,5-diazabicyclo-[4.3.0]nonene-(5) (DBN),1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.21octane(DABCO), etc.). The amount of the compound (7) and the compound (8) isnot critical, but the compound (8) is usually used at least inequivalent amount, preferably 1 to 10 moles, to 1 mole of the compound(7). The reaction is usually carried out at temperature of from about 0°C. to about 200° C., preferably from about 0° C. to about 170° C., forabout 30 minutes to about 30 hours. In the reaction, an alkali metalhalide (e.g. sodium iodide, potassium iodide, etc.) may be added to thereaction system.

The reaction of the compound (7) and the compound (9) is carried out inan appropriate solvent or without solvent in the presence of a reducingagent. The solvent includes, for example, water, alcohols (e.g.methanol, ethanol, isopropanol, etc.), acetonitrile, formic acid, aceticacid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran,etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or amixture of these solvents. The reducing agent includes, for example,formic acid, fatty acid alkali metal salts (e.g. sodium formate, etc.),hydrogenating reducing agents (e.g. sodium boro hydride, sodiumcyanoboro hydride, lithium aluminum hydride, etc.), catalystic reducingagents (e.g. palladium black, palladium-carbon, platinum oxide, platinumblack, Raney nickel, etc.).

When formic acid is used as the reducing agent, the reaction is usuallycarried out at a temperature of from room temperature to about 200° C.,peferably about 50° C. to about 150° C., for about 1 to 10 hours. Theformic acid is usually used in a large excess amount to the compound(7).

When a hydrogenating reducing agent is used, the reaction is usuallycarried out at a temperature of about -30° C. to about 100° C.,preferably about 0° C. to about 70° C., for about 30 minutes to about 12hours. The reducing agent is usually used in an amount of 1 to 20 moles,preferably 1 to 6 moles, to 1 mole of the compound (7). When lithiumaluminum hydride is used as the reducing agent, it is preferable to usea solvent selected from ethers (e.g. diethyl ether, dioxane,tetrahydrofuran, diglyme, etc.) and aromatic hydrocarbons (e.g. benzene,toluene, xylene, etc.).

When a catalytic reducing agent is used, the reaction is usually carriedout under atmospheric pressure to about 20 atm., preferably atmosphericpressure to about 10 atm. under hydrogen atmosphere or in the presenceof a hydrogen donor (e.g. formic acid, ammonium formate, cyclohexene,hydrazine hydrate, etc.) at a temperature of about -30° C. to about 100°C., preferably about 0° C. to about 60° C., for about 1 to 12 hours. Thecatalytic reducing agent is usually used in an amount of about 0.1 to40% by weight, preferably about 1 to 20% by weight, of the amount of thecompound (7). The compound (9) is usually used at least in equivalentamount, preferably equivalent to a large excess amount, to the compound(7). ##STR21## wherein R¹, R², R¹², R¹⁷, R¹⁸, X and W are as definedabove, and R^(11a) is a lower alkyl. ##STR22## wherein R¹, R², R¹¹, Xand W are as defined above, and R^(12a) is a cycloalkyl.

The reaction of the compound (10) and the compound (11) in the ReactionScheme-5A and the reaction of the compound (12) and the compound (13) inthe Reaction Scheme-5B are carried out in the same manner as in thereaction of the compound (7) and the compound (8) in the above ReactionScheme-4.

Besides, the reaction of the compound (10) and the compound (9) in theReaction Scheme-5A is carried out in the same manner as in the reactionof the compound (7) and the compound (9) in the above Reaction Scheme-4.##STR23## wherein R¹, R², R⁴, R¹⁶, R⁶, R⁷, X, W, and A are as definedabove, l is 0 or an integer of 1 to 3, l' and l" are each an integer of1 to 3, provided that l+l' and l+l" are each an integer not more than 3.##STR24## wherein R¹, R², R⁴, R¹⁶, X, W, A, l, l', and l" are as definedabove, and R¹⁹ is a lower alkanoyloxy, R²⁰ is a lower alkanoyloxy,hydroxy or phthalimido, R²¹ is the same as as R¹⁹ and R²⁰, and M is analkali metal (e.g. potassium, sodium, etc.).

The reaction of the compound (1g) and the compound (14) in the ReactionScheme-6A and the reaction of the compound (1 g) and the compound (15)or (16) in the Reaction Scheme-6B can be carried out under the sameconditions as in the reaction of the compound (7) and the compound (8)in the above Reaction Scheme-4. In the reaction, an alkali metal halide(e.g. sodium iodide, potassium iodide, etc.) may be added to thereaction system. ##STR25## wherein R¹, R², R⁴, R¹⁶, W, l, l', l" and Aare as defined above.

The reaction of converting the compound (1j) into the compound (1k) canbe carried out by reacting the compound (1j) with hydrazine in anappropriate solvent or by hydrolyzing the compound (1j). The solventused in the reaction with hydrazine includes water and further the samesolvent as used in the reaction of the compound (2b) and the compound(4) in the above Reaction Scheme-2. The reaction is usually carried outat a temperature of from room temperature to about 120° C., preferablyabout 0° C. to about 100° C., for about 0.5 to 5 hours. Hydrazine isusually used in an amount of at least 1 mole, preferably about 1 to 5moles, to 1 mole of the compound (1j).

The hydrolysis can be carried out in an appropriate solvent or withoutsolvent in the presence of an acid or a basic compound. The solventincludes, for example, water, lower alcohols (e.g. methanol, ethanol,isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.),ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixtureof these solvents. The acid includes, for example, mineral acids (e.g.hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organicacids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.).The basic compound includes, for example, metal carbonates (e.g. sodiumcarbonate, potassium carbonate, etc.), metal hydroxides (e.g. sodiumhydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like.The reaction is usually carried out at a temperature of from roomtemperature to about 200° C., preferably from room temperature to about150° C., for about 10 minutes to 25 hours. ##STR26## wherein R¹, R², R⁴,W, R¹⁶, l, l', l", X, and A are as defined above, and R²² is a loweralkanoyl.

The reaction of the compound (1l) and the compound (17) is carried outunder the same conditions as in the reaction of the compound (7) and thecompound (8) in the Reaction Scheme-4. In the reaction, an alkali metalhalide (e.g. sodium iodide, potassium iodide, etc.) may be added to thereaction system.

The reaction of converting the compound (1m) into the compound (1l) canbe carried out under the same condition as in the hydrolysis of thecompound (1j) in the Reaction Scheme-7. ##STR27## wherein R¹, R², R⁴, W,R¹⁶, I, l', l", and X are as defined above, and R²³ is a lower alkyl, alower alkanoyloxy-substituted lower alkyl, a halogen-substituted loweralkyl, a carboxy-substituted lower alkyl, a carbamoyl-substituted loweralkyl, a hydroxy-substituted lower alkyl, a loweralkoxycarbonyl-substituted lower alkyl, a phthalimido-substituted loweralkyl, an aminocarbonyl-lower alkyl having optionally a lower alkylsubstituent, or a group of the formula: ##STR28## (A, R⁶ and R⁷ are asdefined above).

The reaction of the compound (1n) and the compound (18) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. In the reaction, analkali metal halide (e.g. sodium iodide, potassium iodide, etc.) may beadded to the reaction system. ##STR29## wherein R¹, R², R⁴, W, R¹⁶, R¹⁷,R¹⁸, X, and A are as defined above, and R^(6') is hydrogen atom, a loweralkyl having optionally a hydroxy substituent, a lower alkanoyl, orbenzoyl, R^(7a) is a lower alkyl having optionally a hydroxysubstituent, and R^(7b) is a lower alkanoyl or benzoyl.

The reaction of the compound (1p) and the compound (19) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1p) and the compound (20) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the Reaction Scheme-1.

Besides, the compound (1r) can also be obtained by reacting the compound(1p) with a compound of the formula: (R^(7b))₂ O (R^(7b) is as definedabove). The reaction can be carried out in an appropriate solvent orwithout solvent in the presence or absence, peferably presence, of abasic compound. The solvent includes, for example, the above-mentionedaromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol,etc.), dimethylformamide, dimethylsulfoxide, and further halogenatedhydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone,pyridine, etc. The basic compound includes, for example, tertiary amines(e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassiumhydroxide, sodium hydride, and the like. The above reaction can also becarried out in a solvent such as acetic acid or benzoic acid in thepresence of a mineral acid (e.g. sulfuric acid, etc.). The acidanhydride is usually used in an equimolar amount or more, preferably 1to 10 moles, to 1 mole of the starting compound, and the reaction isusually carried out at a temperature of about 0° C. to about 200° C.,preferably from about 0° C. to about 150° C., for about 0.5 to 15 hours.##STR30## wherein R¹, R², R⁴, R⁹, R¹⁰, W, and B are as defined above.

The reaction of the compound (is) and the compound (21) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR31## wherein R¹,R², R⁴, W, R⁹, R¹⁰, X, and B are as defined above.

The reaction of the compound (1u) and the compound (21) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. In the reaction, analkali metal halide (e.g. sodium iodide, potassium iodide, etc.) may beadded to the reaction system. ##STR32## wherein R¹, R², R⁴, W, and B areas defined above, and R²⁴ is a lower alkyl.

The reaction of the compound (2b) and the compound (22) can be carriedout in an appropriate inert solvent. The inert solvent includes, forexample, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.),ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether,etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol,etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform,carbon tetrachloride, etc.), acetic acid, ethyl acetate, acetonitrile,dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, andthe like. The amount of the compound (2b) and the compound (22) is notcritical, but the compound (22) is usually used in an amount of at leastone mole, preferably 1 to 2 moles, to 1 mole of the compound (2b). Thereaction is usually carried out at a temperature of from about 0° C. toabout 150° C., preferably from about 0° C. to about 100° C., for about30 minutes to about 10 hours.

The esterification of the compound (1w) is usually casried out byreacting the starting compound with an alcohol (e.g. methanol, ethanol,isopropanol, etc.) in the presence of a mineral acid (e.g. hydrochloricacid, sulfuric acid, etc.) and a halogenating agent (e.g. thionylchloride, phosphorus oxychloride, phosphorus pentachloride, phosphorustrichloride, etc.) at a temperature of 0° C. to 150° C., preferably 50°C. to 100° C., for about 1 to 10 hours.

The hydrolysis of the compound (1x) can be carried out under the sameconditions as in the hydrolysis of the compound (1j) in the ReactionScheme-7. ##STR33## wherein R¹, R², R⁴, W, B, M, and X are as definedabove, and R²⁵ is a phenyl which has optionally 1 to 3 substituentsselected from a lower alkyl, a lower alkoxy and an amino havingoptionally a lower alkanoyl substituent, or naphthyl, and R^(25') is aphenoxy which has optionally 1 to 3 substituents selected from a loweralkyl, a lower alkoxy and an amino having optionally a lower alkanoylsubstituent, naphthyloxy or phthalimido.

The reaction of the compound (1u) and the compound (23) or (23a) can becarried out under the same conditions as in the reaction of the compound(7) and the compound (8) in the above Reaction Scheme-4.

The compound (1y) wherein R^(25') is phthalimido can be converted intothe compound (1y) wherein R^(25') is amino under the same conditions asin the reaction of converting the compound (1j) into the compound (1k)in the above Reaction Scheme-7. ##STR34## wherein R¹, R² and R³ are asdefined above, and R²⁶ is oxo, R²⁷ is hydroxy, and W' is the same as W,provided that the substituents on the group --(CH₂)_(p) -- or--CH═CH--(CH₂)_(q) -- are 0 to 2, and R²⁸ and R²⁹ are the same ordifferent and are each hydrogen atom, a lower aikenyl, a cycloalkyl, anoxiranyl-substituted lower alkyl, a lower alkyl having 1 to 2substituents selected from a lower alkoxy, hydroxy and an amino havingoptionally a lower alkyl substituent, a phenyl-lower alkyl, apyridyl-lower alkyl, a cyano-substituted lower alkyl, a loweralkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted loweralkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl which has optionallya phenyl-lower alkyl substituent, an aminocarbonyl-lower alkyl havingoptionally a lower alkyl substituent, or a lower alkyl, or R²⁸ and R²⁹may bind together with the nitrogen atom to which they bond to form a 5-or 6-membered saturated heterocyclic group with or without beingintervened with nitrogen or oxygen atom, which heterocyclic ring mayoptionally have a substituent selected from a lower alkyl, aphenyl-lower alkyl, or a lower alkanoyl.

The conversion of the compound (1A) into the compound (1B) is carriedout by reduction thereof. The reducing reaction is preferably carriedout by using a hydrogenating reducing agent (e.g. lithium aluminumhydride, sodium borohydride, diborane, etc.). The reducing agent isusually used in an amount of at least one mole, preferably 1 to 15moles, to 1 mole of the starting compound. The reducing reaction isusually carried out in an appropriate solvent, for example, water,alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g.tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or amixture of these solvents, at a temperature of from about -60° C. toabout 150° C., peferably about -30° C. to about 100° C., for about 10minutes to 15 hours. When lithium aluminum hydride or diborane is usedas the reducing agent, it is preferable to use an anhydrous solvent suchas tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.

The reaction of converting the compound (1A) into the compound (1C) isusually carried out in an appropriate solvent or without solvent in thepresence or absence of a dehydrating agent. The solvent includes, forexample, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenatedhydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbontetrachloride, etc.), aprotic polar solents (e.g. dimethylformamide,dimethylacetamide, N-methylpyrrolidone, etc.), or a mixture of thesesolvents. The dehydrating agent includes, for example, conventionaldrying agent used for dehydrating solvents (e.g. molecular sieves,etc.), mineral acids (e.g. hydrochloric acid, sulfuric acid, boronetrifluoride, etc.), organic acids (e.g. p-toluenesulfonic acid, etc.),and the like. The reaction is usually carried out at a temperature offrom room temperature to about 250° C., preferably from about 50° C. toabout 200° C., for about 1 to 48 hours. The amount of the compound (24)is not critical, but it is usually used at least in an equivalentamount, preferably equimolar to largely excess to the amount of thecompound (1A). The dehydrating agent is preferably used in a largelyexcess amount in case of the drying agent and in a catalytic amount incase of the acid.

The subsequent reducing reaction can be carried out by various methods,for example by catalytically hydrogenating the compound in anappropriate solvent in the presence of a catalyst. The solvent includes,for example, water, acetic acid, alcohols (e.g. methanol, ethanol,isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.),ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran,diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.),aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture ofthese solvents. The catalyst includes, for example, palladium, palladiumblack, palladium-carbon, platinum, platinum oxide, copper chromite,Raney nickel, and the like. The catalyst is usually used in an amount of0.02 to 1 part by weight to 1 part by weight of the starting tompound.The reaction is usually carried out at a temperature of from about -20°C. to about 100° C., peferably about 0° C. to about 70° C., under ahydrogen atmospheric pressure of 1 to 10 atm. for about 0.5 to 20 hours.

Although the reducting reaction can be carried out under the aboveconditions, it is preferably carried out by using a hydrogenatingreducing agent. The hydrogenating reducing agent includes, for example,lithium aluminum hydride, sodium borohydride, diborane, etc., and it isusually used in an amount of at least one mole, preferably 1 to 10moles, to 1 mole of the compound (1A). The reaction is usually carriedout in an appropriate solvent, such as water, lower alcohols (e.g.methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran,diethyl ether, diglyme, etc.), dimethylformamide, or a mixture of thesesolvents, at a temperature of about -60° C. to about 50° C., preferablyabout -30° C. to room temperature, for about 10 minutes to about 5hours. When lithium aluminum hydride or diborane is used as the reducingagent, it is preferable to use an anhydrous solvent such as diethylether, tetrahydrofuran, diglyme, etc.

The compound (1C) wherein at least one of R²⁸ and R²⁹ is hydrogen atomcan be converted into the compound (1C) wherein at least one of R²⁸ andR²⁹ is a lower alkyl by reacting the compound (1C) with the compound (8)or the compound (9) under the same conditions as in the reaction of thecompound (7) and the compound (8) or (9) in the above Reaction Scheme-4.##STR35## wherein R¹, R², R³, R¹⁴, R¹⁵, W', and M are as defined above,and R³¹ is a phenyl-lower alkyl, and R³⁰ is a lower alkoxycarbonyl.

The reaction of converting the compound (1D) into the compound (1E) canbe carried out under the same conditions as in the reaction ofconverting the compound (1A) into the compound (1B) in the aboveReaction Scheme-15.

The reaction of converting the compound (1D) into the compound (1F) canbe carried out under the same conditions as in the hydrolysis reactionof the compound (1j) in the above Reaction Scheme-7.

The reaction of the compound (1F) and the compound (25) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The halogenation of the compound (1F) can be carried out under aconventional condition for halogenation of a carboxylic acid. Thereaction of the thus-obtained carboxylic acid halide of the compound(1F) with the compound (26) is carried out in an appropriate solvent inthe presence or absence of a basic compound. The solvent includes, forexample, halogenated hydrocarbons (e.g. methylene chloride, chloroform,etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.),ethers (e.g. diethyl ether, tetrahydrofuran, dimethoxyethane, etc.),esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polarsolvents (e.g. N,N-dimethylformamide, dimethylsulfoxide,hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol,propanol, butanol, 3-methoxy-1-butanol, ethyl cellosolve, methylcellosolve, etc.), pyridine, acetone, acetonitrile, water, or a mixtureof these solvents. The basic compound includes, for example, organicbases such as triethylamine, trimethylamine, pyridine, dimethylaniline,N-methylmorpholine, DBN, DBU, DABCO, etc., inorganic bases such aspotassium carbonate, sodium carbonate, potassium hydroxide, sodiumhydroxide, potassium hydride, sodium hydride, silver carbonate,alcoholates (e.g. sodium methylate, sodium ethylate, etc.), and thelike. The compound (26) is usually used in an amount of at least 1 mole,preferably 1 to 1.5 mole, to 1 mole of the carboxylic acid halide of thecompound (1F). The reaction is usually carried out at a temperature offrom -30° C. to about 180° C., preferably from about 0° C. to about 150°C., for about 5 minutes to 30 hours.

The reaction of the compound (1H) and the compound (27) is carried outin an appropriate solvent or without solvent at a temperature of fromabout 0° C. to about 200° C., preferably from room temperature to about150° C. The solvent includes the same solvents as used in the abovereaction of the carboxylic acid halide of the compound (1F) and thecompound (26). The compound (27) is preferably used in an amount largelyexcess to the the compound (1H). The reaction is usually completed in areaction time of about 1 to 5 hours.

The reaction of converting the compound (1I) into the compound (1J) canbe carried out by reducing the compound. The reducing reaction isusually carried out by catalytically hydrogenating the compound in anappropriate solvent in the presence of a catalyst. The solvent includes,for example, water, acetic acid, alcohols (e.g. methanol, ethanol,isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.),ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycoldimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate,etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, etc.), aceticacid, or a mixture of these solvents. The catalyst includes, forexample, palladium, palladium black, palladium-carbon, platinum,platinum oxide, copper chromite, Raney nickel, and the like. Thecatalyst is usually used in an amount of 0.02 to 1 part by weight to 1part by weight of the starting compound. The reaction is usually carriedout at a temperature of from about -20° C. to about 100° C., peferablyabout 0° C. to about 80° C., under a hydrogen atmospheric pressure of 1to 10 atm. for about 0.5 to 20 hours. ##STR36## wherein R¹, R², R³, W',l, R¹⁷, R¹⁸, and X are as defined above, and R^(14a) is hydrogen atom, alower alkyl, a lower alkanoyl, a lower alkenyl, a cycloalkyl, anoxiranyl-substituted lower alkyl, a lower alkyl having 1 to 2substituents selected from a lower alkoxy, hydroxy and an amino havingoptionally a lower alkyl substituent, a phenyl-lower alkyl, apyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, a loweralkoxycarbonyl, anilinocarbonyl, an amino-carbonyl having optionally alower alkyl substituent, a cyano-substituted lower alkyl, a loweralkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted loweralkyl, a carboxy-substituted lower alkyl, atetrahydro-pyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent, a halogen-substituted lower alkanoyl, animiazolyl-substituted lower alkanoyl, an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl, an aminocarbonyl-lower alkyl having optionally a loweralkyl substituent, or a phenyl-lower alkoxycarbonyl, R^(15a) is a loweralkyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkylhaving 1 to 2 substituents Selected from a lower alkoxy, hydroxy and anamino having optionally a lower alkyl substituent, a phenyl-lower alkyl,a pyridyl-lower alkyl, a lower alkylsulfonyl, a cyano-substituted loweralkyl, a lower alkoxycarbonyl-substituted lower alkyl, acarbamoyl-substituted lower alkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent, an amino-carbonyl-lower alkyl havingoptionally a lower alkyl substituent, or a lower alkenyl, and R^(15b) isa lower alkanoyl, a phenyl-lower alkoxycarbonyl, benzoyl, a loweralkoxycarbonyl, a halogen-substituted lower alkanoyl, animidazolyl-substituted lower alkanoyl, or an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl.

The reaction of the compound (1K) and the compound (28) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1K) and the compound (29) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. The compound (1M) canalso be obtained by reacting the compound (1K) with a compound of theformula (R^(15b))₂ O (wherein R^(15b) is as defined above). The reactioncan be carried out under the same conditions as in the reaction of thecompound (1p) and the compound of the formula: (R^(7b))₂ O as describedhereinbefore.

The compound (1M) wherein R^(15b) is formyl can also be prepared byreacting the compound (1K) with a formate of the formula: HCOOR⁸² (R⁸²is a lower alkyl). The reaction is usually carried out in the solvent asused in the reaction of the compound (7) and the compound (8) in theabove Reaction Scheme-4 or without solvent, at a temperature of about 0°C. to about 200° C., preferably about 0° C. to about 170° C., for about30 minutes to about 30 hours. The formate is preferably used in alargely excess amount to the compound (1K). ##STR37## wherein R¹, R²,R⁴, R¹⁶, W, l, l' and l" are as defined above, and R³² is a loweralkoxycarbonyl-substituted lower alkoxy, R³³ is a carbamoyl-substitutedlower alkoxy, R³⁴ is a carboxy-substituted lower alkoxy, R⁴⁴ is an aminohaving optionally a lower alkyl substituent, and R⁴⁵ is anaminocarbonyl-lower alkoxy having optionally a lower alkyl substituent.

The conversion of the compound (1N) into the compound (1O) can becarried out by reacting the compound with aqueous ammonia in anappropriate solvent in an autoclave. The solvent includes the samesolvents as used in the reaction of the carboxylic acid halide and theamine (2) in the above Reaction Scheme-1. The aqueous ammonia is used ina largely excess amount to the compound (1N). The reaction proceedsadvantageously by adding an ammonium halide (e.g. ammonium chloride,etc.) to the reaction system. The reaction is usually carried out at atemperature of from room temperature to about 200° C., preferably fromroom temperature to about 150° C., for about 1 to 10 hours.

The reaction of converting the compound (1N) into the compound (1P) canbe carried out under the same conditions as in the hydrolysis of thecompound (1j) in the above Reaction Scheme-7.

The reaction of the compound (1P) and the compound (30) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR38## wherein R¹,R², R⁴, R¹⁶, W, l, l' and l" are as defined above.

The reducing reaction in the above reaction scheme is usually carriedout, for example, (i) with a reducing catalyst in an appropriate solventor (ii) with a reducing agent such as a mixture of a metal or metal saltwith an acid, or a mixture of a metal or metal salt with an alkali metalhydroxide, a sulfide or an ammonium salt in an appropriate inertsolvent.

In case of using a reducing catalyst, the solvent includes, for example,water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol,etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g.dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethylether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aproticpolar solvents (e.g. N,N-dimethylformamide, etc.), or a mixture of thesesolvents. The catalyst includes, for example, palladium, palladiumblack, palladium-carbon, platinum, platinum oxide, copper chromite,Raney nickel, and the like. The catalyst is usually used in an amount of0.02 to 1 part by weight to 1 part by weight of the starting compound.The reaction is usually carried out at a temperature of from about -20°C. to about 150° C., peferably about 0° C. t0 about 100° C., under ahydrogen pressure of 1 to 10 atm. for about 0.5 to 10 hours. In thereaction, an acid such as hydrochloric acid may optionally added to thereaction system.

In case of the above method (ii), the reducting agent includes a mixtureof iron, zinc, tin or stannous chloride and-a mineral acid (e.g.,hydrochloric acid, sulfuric acid, etc.), or a mixture of iron, ferroussulfate, zinc or tin and an alkali metal hydroxide (e.g. sodiumhydroxide, etc.), a sulfide (e.g. ammonium sulfide, etc.), aqueousammonia, or an ammonium salt (e.g. ammonium chloride, etc.). The inertsolvent includes, for example water, acetic acid, methanol, ethanol,dioxane, and the like. The reducing reaction conditions are determineddepending on the kinds of the reducting agent, but in case of using areducing agent comprising stannous chloride and hydrochloric acid, forexample, it is preferably carried out at a temperature of about 0° C. toroom temperature for about 0.5 to 10 hours. The reducing agent isusually used in an amount of at least one mole, preferably 1 to 5 moles,to 1 mole of the starting compound. ##STR39## wherein R¹, R², R⁴, R¹⁶,R¹⁷, R¹⁸, l, l', l" and W are as defined above, and R³⁶ is a loweralkyl, R³⁷ is a lower alkanoyl, and R³⁵ is hydrogen atom, a lower alkylor a lower alkanoyl.

The reaction of the compound (1S) and the compound (31) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1S) and the compound (32) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. Besides, the compound(1U) can also be obtained by reacting the compound (1S) with a compoundof the formula: (R³⁷)₂ O (R³⁷ is as defined above). The reaction iscarried out under the same conditions as in the above reaction of thecompound (1p) and a compound of the formula: (R^(7b))₂ O.

The compound (1) wherein R⁸ is a phenyl-lower alkoxycarbonyl can beconverted into the compound (1) wherein R⁸ is hydrogen atom in the samemanner as in the reaction of converting the compound (1I) into thecompound (1J) in the above Reaction Scheme-16.

Other derivatives of the starting compound (2) can be prepared, forexample, by the process as shown in the following reaction scheme.##STR40## wherein R¹, R², and W are as defined above

The reaction of the compound (2) and the compound (33) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of converting the compound (34) into the compound (2a) canbe carried out under the same conditions as in the reducing reaction inthe above Reaction Scheme-19.

The starting compound (5) can be prepared, for example, by the processof the following reaction scheme. ##STR41## wherein R¹, R² and W are asdefined above, and R³⁸ is a lower alkyl.

The reaction of the compound (2) and the compound (35) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of converting the compound (36) into the compound (5) canbe carried out under the same conditions as in the hydrolysis reactionin the above Reaction Scheme-7. ##STR42## wherein R¹ , R² , R⁴ , R¹⁶, l,l', l", X, and W are as defined above, and R³⁹ is a lower alkanoyl.

The reaction of the compound (1W) and the compound (37) can be carriedout under the same conditions as in the reaction of the compound (1n)and the compound (18) in the above Reaction Scheme-9.

The hydrolysis reaction of the compound (iX) can be carried out underthe same conditions as in the hydrolysis of the compound (1j) in theabove Reaction Scheme-7. ##STR43## wherein R¹, R², R⁴, R¹⁶, l, l', l",and W are as defined above, R⁴⁰ is a lower alkanoyl, and R⁴¹ is ahydroxy-substituted lower alkyl.

The reaction of converting the compound (1Y) into the compound (1Z) canbe carried out under the same conditions as in the reaction ofconverting the compound (1A) into the compound (1B) in the aboveReaction Scheme-15. ##STR44## wherein R¹, R², R⁴, R¹⁶, l, l', l", and Ware as defined above, R⁴² is a lower alkoxycarbonyl and R⁴³ is carboxyl.

The reaction of converting the compound (1aa) into the compound (1bb)can be carried out under the same conditions as in the hydrolysis of thecompound (1j) in the above Reaction Scheme-7.

The esterification reaction of the compound (1bb) can be carried outunder the same conditions as in the esterification of the compound (1w)in the above Reaction Scheme-13. ##STR45## wherein R¹, R², R⁴, and W areas defined above, and R⁴⁶ is a phenyl having optionally a lower alkylsubstituent.

The reaction of the compound (2b) and the compound (38) is usuallycarried out in an appropriate solvent or without solvent in the presenceOr absence, preferably in the absence, of a basic compound. The solventand basic compound are the same as those used in the reaction of thecarboxylic acid halide and the amine (2) in the above Reaction Scheme-1.

The compound (38) is usually used in an amount of about 1 to 5 moles,preferably about 1 to 3 moles, to 1 mole of the compound (2b). Thereaction is usually carried out at a temperature of from about 0° C. toabout 200° C., preferably from room temperature to about 150° C., forabout 5 minutes to about 30 hours. In the reaction, a boron compound(e.g. boron trifluoride etherate, etc.) may be added to the reactionsystem. ##STR46## wherein R¹, R², R⁴, W, and X are as defined above, andR⁴⁷ is a phenylsulfonyl which has optionally a substituent selected froma halogen atom and a lower alkyl on the phenyl ring, orquinolylsulfonyl.

The reaction of the compound (2b) and the compound (39) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR47## wherein R¹,R², R⁴, W, R¹⁷, R¹⁸, and X are as defined above, R⁴⁸ is a phenyl-loweralkoxycarbonyl, a lower alkanoyl, an amino-lower alkanoyl havingoptionally a lower alkyl substituent, and R⁴⁹ is a lower alkyl or acarbamoyl-lower alkyl.

The reaction of the compound (1ee) and the compound (40) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1ee) and the compound (41) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4, provided that in the reaction product (1ff) producedby the reaction of the compound (1ee) and the compound (9), the groupR⁴⁹ is a lower alkyl. ##STR48## wherein R¹, R², R⁵, and W are as definedabove, and R⁵⁰ is a benzoyl having optionally a halogen substituent onthe phenyl ring.

The reaction of the compound (7) and the compound (42) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR49## wherein R¹,W', R²⁶, R², and R³ are as defined above, R¹⁰³ is hydroxy or sulfoxy,and R⁵¹ is hydroxyimino or sulfoxyimino.

The reaction of the compound (1A) and the compound (43) is usuallycarried out in an appropriate inert solvent in the presence or absenceof a basic compound. The basic compound includes, for example, inorganicbasic compounds such as sodium hydroxide, potassium hydroxide, sodiumcarbonate, potassium carbonate, etc., and organic basic compounds suchas piperidine, pyridine, triethylamine, 1,5-diazabicyclo[4.3.0]nonene-5(DBN), 1,8-diazabicyclo-[5.4.0]undecene-7 (DBU),1,4-diazabicyclo[2.2.21octane (DABCO), etc. The inert solvent includes,for example, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, ethylene glycolmonomethyl ether, etc.), aromatic hydrocarbons (e.g. benzene, toluene,xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane,dichloroethane, chloroform, carbon tetrachloride, etc.), pyridine,dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide,etc., or a mixture of these solvents. The compound (43) is usually usedat least in equivalent amount, preferably 1 to 5 moles, to 1 mole of thecompound (1A). The reaction is usually carried out at a temperature offrom room temperature to about 200° C., preferably from about 50° C. to150° C., for about 1 to 10 hours. ##STR50## wherein R¹, W', R²⁷, R², M,and R³ are as defined above, and R⁵² is a halogen atom.

The halogenation of the compound (1B) is usually carried out in anappropriate solvent or without solvent by reacting the compound (1B)with a halogenating agent.

The halogenating agent includes mineral acids (e.g. hydrochloric acid,hydrobromic acid, etc.), N,N-diethyl-1,2,2-trichlorovinylamide,phosphorus pentachloride, phosphorus pentabromide, phosphorusoxychloride, thionyl chloride, methanesulfonyl chloride, or acombination of a phenyl-lower alkyl halide (e.g. p-toluenesulfonylchloride, etc.) and a basic compound. The basic compound includes thesame compounds as used in the reaction of the compound (1A) and thecompound (43) in the above Reaction Scheme-30. The solvent includes, forexample, ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenatedhydrocarbons (e.g. chloroform, methylene chloride, carbon tetrachloride,etc.), and the like. The amount of the halogenating agent may varydepending on the kinds of the halogenating agents, and in case of acombination of a phenyl-lower alkyl halide (e.g. p-toluenesulfonylchloride, etc.) and a basic compound, it is used in an amount of atleast 1 mole, preferably 1 to 2 moles, to 1 mole of the compound (1B),and in case of other halogenating agents, it is used at least in anequimolar amount, usually in a largely excess amount, to the compound(1B). The reaction is usually carried out at a temperature of from roomtemperature to about 150° C., preferably from room temperature to about80° C., for about 1 to 80 hours.

The reaction of the compound (1jj) and the compound (44) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reducing reaction of the compound (1kk) can be carried out under thesame conditions as in the reducing reaction using a reducing catalystfor converting the compound (1A) into the compound (1C) in the aboveReaction Scheme-15. ##STR51## wherein R¹, W', R², R³, R²⁷, X, and A areas defined above, R⁵³ is a lower alkanoyloxy having optionally a halogensubstituent, R⁵⁴ is a lower alkoxy, an amino-lower alkanoyloxy havingoptionally a lower alkyl substituent, or a group of the formula:##STR52## (A, R⁸² and R⁸³ are as defined above), R⁵⁵ is a loweralkoxycarbonyl-substltuted lower alkoxy, R⁵⁶ is a carboxy-substitutedlower alkoxy, R⁵⁷ is an aminocarbonyl-lower alkoxy having optionally alower alkyl substituent, R^(54a) is a lower alkyl, an amino-loweralkanoyl having optionally a lower alkyl substituent, or a group of theformula: ##STR53## (A, R⁸² and R⁸³ are as defined above), R^(55a) is alower alkoxy-carbonyl-substituted lower alkyl, R⁵⁸ and R⁵⁹ are the sameor different and are each hydrogen atom or a lower alkyl, and R^(22a) isa lower alkanoyl having optionally a halogen substituent. ##STR54##wherein R¹, W', R², R³, X, R²⁷, and A are as defined above, and R⁶¹ andR⁶² are the same or different and are each hydrogen atom, a lower alkylor a lower alkanoyl.

The reaction of the compound (1B) and the compound (45) or the compound(46) in the Reaction Scheme-32A can be carried out under the sameconditions as in the reaction of the compound (1n) and the compound (18)in the above Reaction Scheme-9.

The reaction of the compound (1B) and the compound (47) and the reactionof the compound (1B) and the compound (48) can be carried out under thesame conditions as in the reaction of the compound (1n) and the compound(18) in the above Reaction Scheme-9.

The reaction of converting the compound (1oo) into the compound (1pp)can be carried out under the same conditions as in the hydrolysisreaction of the compound (1j) in the above Reaction Scheme-7.

The reaction of the compound (1oo) and the compound (49) and thereaction of the compound (1pp) and the compound (49) can be carried outunder the same conditions as in the reaction of the compound (2) and thecompound (3) in the above Reaction Scheme-1.

The reaction of the compound (1B) and the compound (49a) in the ReactionScheme-32B can be carried out under the same conditions as in thereaction of the compound (1n) and the compound (18) in the aboveReaction Scheme-9. ##STR55## wherein R¹, W', R², R³, R²⁷, R⁶¹, R⁶², M,and X are as defined above, R⁶⁰ is a halogen-substituted lower alkyl,R⁶⁴ is a phthalimido-substituted lower alkyl, R⁶³ is an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, or a phthalimido-substituted lower alkoxy, and R⁶⁵ is anamino-substituted lower alkyl.

The reaction of the compound (1B) and the compound (50) and the reactionof the compound (1B) and the compound (52) can be carried out under thesame conditions as in the reaction of the compound (1n) and the compound(18) in the above Reaction Scheme-9.

The reaction of the compound (1rr) and the compound (51) or the compound(23a) can be carried out under the same conditions as in the reaction ofthe compound (1g) and the compound (14) in the above Reaction Scheme-6.

The reaction of converting the compound (1tt) into the compound (1uu)can be carried out under the same conditions as in the reaction ofconverting the compound (1j) into the compound (1k) in the aboveReaction Scheme-7. ##STR56## wherein R¹, R², R³, R⁶¹, W', A, R¹⁷, R¹⁸,and X are as defined above, R^(62a) is a lower alkyl, and R^(62b) is alower atkanoyl.

The reaction of the compound (1vv) and the compound (53) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1vv) and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1vv) and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10. ##STR57## wherein R¹, R², R³, and W' are as defined above,R^(58') and R^(59') are the same or different and are each hydrogenatom, a lower alkyl, or a lower alkanoyl.

The reaction of converting the compound (1yy) into the compound (1zz) isusually carried out by reducing the compound (1yy).

The reducting reaction is preferably carried out by using ahydrogenating reducing agent. The hydrogenating reducing agent includes,for example, lithium aluminum hydride, sodium boro hydride, diborane,etc. The reducing agent is usually used in an amount of at least onemole, preferably 1 to 15 moles, to 1 mole of the starting compound. Thereducing reaction is usually carried out in an appropriate solvent, suchas water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),ethers (e.g. tetra-hydrofuran, diethyl ether, diisopropyl ether,diglyme, etc.), or a mixture of these soslvents, at a temperature ofabout -60° C. to about 150° C., preferably about -30° C. to 100° C., forabout 10 minutes to about 5 hours. When lithium aluminum hydride ordiborane is used as the reducing agent, it is preferable to use ananhydrous solvent such as diethyl ether, tetrahydrofuran, diglyme, etc.##STR58## wherein R¹, W', R², R³, R^(62a), R^(62b), X, R¹⁷, R¹⁸, and Aare as defined above, R^(58a) is hydrogen atom, a lower alkyl or a loweralkanoyl.

The reaction of the compound (1AA) and the compound (53) or the compound(9) can be carried out under the same conditions as in the reaction ofthe compound (7) and the compound (8) or the compound (9) in the aboveReaction Scheme-4.

The reaction of the compound (1AA) and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1AA) and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10.

The compound (1BB) wherein R^(62b) is formyl can also be prepared byreacting the compound (1AA) with a formate of the formula: HCOOR⁸² underthe same conditions as in the reaction of the compound (1K) and thecompound of the formula: HCOOR⁸² as described hereinbefore.

The compounds of the formula (1) wherein W is sulfur atom or sulfinyl,or R⁸² and R⁸³ bind together with the nitrogen atom to which they bondto form thiomorpholino or 1-oxo-thiomorpholino can be converted into thecorresponding compounds of the formula (1) wherein W is sulfinyl orsulfonyl, or R⁸² and R⁸³ bind together with the nitrogen atom to whichthey bond to form 1-oxo-thiomorpholino or 1,1-dioxo-thiomorpholino,respectively, by oxidation thereof.

The oxidation reaction is carried out in an appropriate solvent in thepresence of an oxidizing agent. The solvent includes, for example,water, organic acids (e.g. formic acid, acetic acid, trifluoroaceticacid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenatedhydrocarbons (e.g. chloroform, dichloromethane, etc.), or a mixture ofthese solvents. The oxidizing agent includes, for example, peracids(e.g. performic acid, peracetic acid, trifluoro-peracetic acid,perbenzoic acid, m-chloro-perbenzoic acid, o-carboxy-perbenzoic acid,etc.), hydrogen peroxide, sodium metaperiodate, dichromic acid,dichromates (e.g. sodium dichromate, potassium dichromate, etc.),permanganic acid, permanganates (e.g. potassium permanganate, sodiumpermanganate, etc.), lead salts (e.g. lead tetraacetate, etc.), and thelike. The oxidizing agent is usually used in an amount of at least 1mole, preferably 1 to 2 moles, to 1 mole of the starting compound.Besides, in cases of the oxidation of converting the sulfur atom intosulfonyl group, the oxidizing agent is usually used at least 2 moles,preferably 2 to 4 moles, to 1 mole of the starting compound. The abovereaction is usually carried out at a temperature of about -10° C. toabout 40° C., preferably from about -10° C. to room temperature, forabout 1 to 100 hours.

The compound (1) wherein R¹⁶ or R² is a lower alkoxy can be convertedinto the correspond compound (1) wherein R¹⁶ or R² is hydroxy by heatingthe compound in a mixture of an acid (e.g. hydrobromic acid,hydrochloric acid, etc.) and a solvent (e.g. water, methanol, ethanol,isopropyl alcohol, etc.) at 30° to 150° C., preferably at 50° to 120° C.

Besides, the compound (1) wherein R¹⁶ or R² is hydroxy can also beprepared by hydrolysis of the above compound (1) wherein R¹⁶ or R² is alower alkoxy. The hydrolysis can be carried out in an appropriatesolvent in the presence of an acid. The solvent includes, for example,water, lower alcohols (e.g. methanol, ethanol, isopropyl alcohol, etc.),ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons(e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polarsolvents (e.g. acetonitrile, etc.), or a mixture of these solvents. Theacid includes, for example, mineral acids (e.g. hydrochloric acid,hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminumchloride, boron tribromide, etc.), iodides (e.g. sodium iodide,potassium iodide, etc.), or a mixture of the above Lewis acid andiodide. The reaction is usually carried out at a temperature of fromroom temperature to about 150° C., preferably from room temperature toabout 100C, for about 0.5 to 30 hours. ##STR59## wherein R¹, R², R³,R^(62b), and W' are as defined above, R^(51a) is hydroxyimino, and R⁶⁶is a lower alkanoyloxyimino.

The reaction of the compound (1ii') and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1ii') and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10. ##STR60## wherein R¹, R², R³, W', R²⁶, R¹⁴, R¹⁵, R^(62b), Xand M are as defined above, R⁶⁷ is methylidene, R⁶⁸ is a group of theformula: ##STR61## and R⁶⁹ is a group of the formula: ##STR62## (R¹⁴ andR¹⁵ are as defined above), or ##STR63## is an amino having optionally asubstituent selected from a lower alkyl and a lower alkanoyl, is a loweralkylsulfonyl, and W" is the same as the above W, provided that thenumber of the substituent in the groups --(CH₂)_(p) -- and--CH═CH--(CH₂)_(q) -- is 0 or 1.

The reaction of converting the compound (1A) into the compound (1EE) iscarried out in an appropriate solvent in the presence of a Wittigreagent and a basic compound. The Wittig reagent includes, for example,a phosphoric compound of the formula:

    [(R.sup.71).sub.3 P.sup.+ --CH.sub.2 --R.sup.72 ]X.sup.-   (A)

wherein R⁷¹ is phenyl, R⁷² is hydrogen atom or a lower alkyl, and X is ahalogen atom. The basic compound includes inorganic bases (e.g. metallicsodium, metallic potassium, sodium hydride, sodium amide, sodiumhydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,sodium hydrogen carbonate, etc.), metal alcoholates (e.g. sodiummethylate, sodium ethylate, potassium t-butoxide, etc.), alkyl or aryllithiums or lithium amides (e.g. methyl lithium, n-butyl lithium, phenyllithium, lithium diisopropylamide, etc.), organic bases (e.g. pyridine,piperidine, quinoline, triethylamine, N,N-dimethylaniline, etc.). Thesolvent includes any solvent which does not affect on the reaction, forexample, ethers (e.g. diethyl ether, dioxane, tetra-hydrofuran,monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene,xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane,cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.),aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide,hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol,isopropanol, etc.), and the like. The reaction is usually carried out ata temperature of about -80° C. to about 150° C., preferably about -80°C. to about 120° C., for about 0.5 to 15 hours.

The reaction of converting the compound (1EE) into the compound (1LL)can be carried out under the same conditions as in the catalyticallyhydrogenation reaction for converting the compound (1A) into thecompound (1C) in the above Reaction Scheme-15.

The reaction of converting the compound (1EE) into the compound (1FF) iscarried out under the same conditions as in the reaction of convertingthe compound (1) wherein W is sulfur atom or sulfinyl into thecorresponding compound (1) wherein W is sulfinyl or sulfonylrespectively as described herebefore.

The reaction of the compound (1FF) and the compound (25) can be carriedout un° der the same conditions as in the reaction of the compound (7)and the compound (8) in the above Reaction Scheme-4.

The reaction of converting the compound (1EE) into the compound (1E) canbe carried out by firstly subjecting it to hydroboration reaction andthen to oxidation.

The hydroboration reaction is carried out in a solvent such as ethers(e.g. diethyl ether, tetrahydrofuran, dioxane, etc.) in the presence ofa hydroborating agent at a temperature of from about 0° C. to about 50°C., preferaly about 0° C. to room temperature, for about 1 to 10 hours.The hydroborating agent includes boron hydride compounds, for example,BH₃.tetrahydrofuran, ##STR64## and the like.

The subsequent oxidation is carried out in water in the presence of anoxidizing agent. The oxidizing agent includes, for example, alkalinehydrogen peroxides (e.g. hydrogen peroxide--sodium hydroxide, etc.), andair oxidation is also used. The reaction is usually carried out at atemperature of from room temperature to about 150° C., preferably fromroom temperature to about 100° C., for 0.5 to 7 hours.

The hydroborating agent and the oxidizing agent are each used in anamount of at least 1 mole, preferably 1 to 2 mole, to 1 mole of thecompound (1EE).

The reaction of the compound (1E) and the compound (54) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The reaction of the compound (1E) and the compound (55) can be carriedout under the same conditions as in the reaction of the compound (1p)and the compound of the formula: (R^(7b))₂ O in the above ReactionScheme-10.

The reaction of the compound (1E) and the compound (56) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of the compound (1HH) and the compound (44) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reducing reaction of the compound (1JJ) can be carried out under thesame conditions as in the catalytic hydrogenation reaction forconverting the compound (1A) into the compound (1C) in the aboveReaction Scheme-15.

The reaction of converting the compound (1EE) into the compound (1MM)can be carried out by reacting with an oxidizing agent in an appropriatesolvent in the presence of a co-oxidizing agent.

The solvent used for the reaction with an oxidizing agent includes, forexample, pyridine, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether,etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.),halogenated hydrocarbons (e.g. dichloromethane, dichloroethane,chloroform, carbon tetrachloride, etc.), esters (e.g. ethyl acetate,etc.), water, alcohols (e.g. methanol, ethanol, isopropanol, t-butanole,etc.), or a mixture of these solvents. The co-oxidizing agent includes,for example, organic amine N-oxides (e.g. pyridine N-oxide,N-ethyldiisopropylamine N-oxide, N-methylmorpholine N-oxide,trimethylamine N-oxide, triethylamine N-oxide, etc.). The oxidizingagent includes, for example, osmium tetraoxide, and the like. Theoxidizing agent is usually used in an amount of at least 1 mole,preferably 1 to 5 moles, to 1 mole of the starting compound. Thereaction is usually carried out at a temperature of from -20° C. to 150°C., preferably from room temperature to 100° C., for about 1 to 10hours. ##STR65## wherein R¹, R², R³, R²⁷, W', M, and X are as definedabove, R⁷³ is an aminocarbonyl having optionally a lower alkylsubstituent, R⁷⁴ is an aminocarbonyloxy having optionally a lower alkylsubstituent, R⁷⁴ ' is a lower alkyl.

The reaction of the compound (1A) and the compound (57) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of the compound (1A) and the compound (59) is carried outin an appropriate solvent in the presence of an acid. The solventincludes the same solvent as used in the reaction of the compound (7)and the compound (8) in the above Reaction Scheme-4. The acid includes,for example, mineral acids (e.g. hydrochloride acid, sulfuric acid,etc.), sulfonic acids (e.g. methanesulfonic acid, p-toluenesulfonicacid, etc.), alkanoic acids (e.g. trifluoroacetic acid, etc.), and thelike. The compound (59) is used in an amount of at least 1 mole,preferably 1 to 5 moles, to 1 mole of the compound (1A). The reaction isusually carried out at a temperature of from room temperature to about150° C., preferably from room temperature to about 100° C., for about 1to 7 hours.

The reaction of the compound (1A) and the compound (58) can be carriedout under the same conditions as in the reaction of the compound (2b)and the compound (38) in the above Reaction Scheme-26. ##STR66## whereinR¹, R², R³, X, and q are as defined above, and R⁷⁵, R⁷⁶ and R⁷⁷ are eacha lower alkyl, and the carbon atom in the formula: --(CH₂)_(q) -- may besubstituted by oxygen atom, sulfur atom, sulfinyl, sulfonyl, or a groupof the formula: ##STR67## (R¹³ is as defined above), and further thegroup: --(CH₂)_(q) -- may optionally have 1 to 3 substituents selectedfrom a lower alkyl having optionally a hydroxy substituent, a loweralkoxy-carbonyl, carboxyl, hydroxy, oxo, a lower alkanoyloxy havingoptionally a halogen substituent, an amino-lower alkyl having optionallya substituent selected from a lower alkyl and a lower alkanoyl, a loweralkanoyloxy-substituted lower alkyl, a lower alkylsulfonyloxy-loweralkyl, an azido-lower alkyl, a group of the formula: ##STR68## anaminocarbonyloxy having optionally a lower alkyl substituent, a loweralkoxy, a lower alkoxy-carbonyl-substituted lower alkoxy, acarboxy-substituted lower alkoxy, an aminocarbonyl-lower alkoxy havingoptionally a lower alkyl substituent, an amino-lower, alkoxy havingoptionally a substituent selected from a lower alkyl and a loweralkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, a loweralkanoyloxyimino, a lower alkylidene, a halogen atom, azido,sulfoxyimino a group of the formula: ##STR69## (R⁸¹ is hydrogen atom ora lower alkyl), hydrazino, pyrrolyl, an amino-lower alkanoyloxy havingoptionally a lower alkyl substituent, a group of the formula: ##STR70##(A is as defined above, and R⁸² and R⁸³ are the same or different andare each hydrogen atom, a lower alkyl, a carbamoyl-substituted loweralkyl, a hydroxy-substituted lower alkyl, or a pyridyl-lower alkyl, orR⁸² and R⁸³ may bind togeEher with nitrogen atom to which they bond toform a 5- or 6-membered saturated heterocyclic group with or withoutbeing intervened with nitrogen, oxygen or sulfur atom wherein theheterocyclic group has optionally a substituent selected from oxo, alower alkyl, a lower alkanoyl, and carbamoyl), and a group of theformula: ##STR71## (n is as defined above, and R¹⁴ and R¹⁵ are the sameor different and are each hydrogen atom, a lower alkyl, a lower alkenyl,a lower alkanoyl, a cycloalkyl, an oxiranyl-substituted lower alkyl, alower alkyl having 1 to 2 substituents selected from a lower alkoxy,hydroxy and an amino having optionally a lower alkyl substituent, aphenyl-lower alkyl, a pyridyl-lower alkyl, a lower alkylsulfonyl,benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, an aminocarbonylhaving optionally a lower alkyl substituent, a cyano-substituted loweralkyl, a lower alkoxycarbonyl-substituted lower alkyl, acarbamoyl-substituted lower alkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted lower alkanoyl, an imidazolyl-substituted loweralkanoyl, an amino-lower alkanoyl having optionally a substituentselected from a lower alkyl and a lower alkoxycarbonyl, anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ may bind together withthe nitrogen atom to which they bond to form a 5- or 6-memberedsaturated heterocyclic group with or without being intervened withnitrogen or oxygen atom, which heterocyclic group may optionally have asubstituent selected from a lower alkyl, a phenyl-lower alkyl and alower alkanoyl.

The reaction of the compound (1OO) and the compound (60) is carried outin an appropriate solvent in an autoclave. The solvent includes anysolvent as used in the reaction of the compound (7) and the compound (8)in the above Reaction Scheme-4. The reaction is usually carried out at atemperature of from room temperature to about 200° C., preferably fromroom temperature to about 150° C., for about 1 to 7 hours.

The subsequent deamination reaction is carried out in an appropriatesolvent in the presence of a basic compound. The solvent includes thesame solvent as used in the above reaction of the compound (1OO) and thecompound (60). The basic compound includes any basic compound as used inthe reaction of converting the compound (1A) into the compound (1EE) inthe above Reaction Scheme-38. The reaction is usually carried out at atemperature of from room temperature to about 150° C., preferably fromroom temperature to about 100° C., for about 1 to 10 hours. ##STR72##wherein R¹, R², R³ R¹⁴, M, and W' are as defined above, R⁷⁸ is anoxiranyl-substituted lower alkyl, R⁷⁹ is a lower alkoxy, or an aminohaving optionally a lower alkyl substituent, and R⁸⁰ is a lower alkylhaving 2 substituents selected from hydroxy, a lower alkoxy, and anamino having optionally a lower alkyl substituent.

The reaction of the compound (1QQ) and the compound (61) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4.

The reaction of the compound (1QQ) and the compound (62) can be carriedout by firstly reacting them in trifluoroacetic acid at a temperature ofabout 0° C. to about 100° C., preferably about 0° C. to about 50° C.,for about 1 to 7 hours, followed by hydrolysis of the resultant.

The hydrolysis is carried out in an appropriate solvent or withoutsolvent in the presence of an acid or a basic compound. The solventincludes, for example, water, lower alcohols (e.g. methanol, ethanol,isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.),ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixtureof these solvents. The acid includes, for example, mineral acids (e.g.hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids(e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.), and thelike. The basic compound includes, for example, metal carbonates (e.g.sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g.sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.). Thereaction is usually carried out at a temperature of from roomtemperature to about 200° C., preferably from room temperature to about150° C., for about 0.5 to 25 hours. ##STR73## wherein R¹, R², R³, and W'are as defined above, and R⁸¹ is hydroxyimino or a loweralkanoyloxyimino.

The reaction of converting the compound (1SS) into the compound (1ll) iscarried out by catalytically hydrogenating the compound (1SS) in anappropriate solvent in the presence of a catalyst. The solvent includes,for example, water, acetic acid, alcohols (e.g. methanol, ethanol,isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.),ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran,diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.),aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture ofthese solvents. The catalyst includes, for example, palladium, palladiumblack, palladium-carbon, platinum, platinum oxide, copper chromate,Raney nickel, and the like. The catalyst is usually used in an amount of0.02 to 1 part by weight to 1 part by weight of the compound (1SS). Thereaction is usually carried out at a temperature of from about -20° C.to about 100oC, peferably about 0° C. to about 70° C., under a hydrogenatmospheric pressure of 1 to 10 atm. for about 0.5 to 20 hours.

Alternatively, the reducing reaction can also be carried out by using ahydrogenating reducing agent. The hydrogenating reducing agent includes,for example, lithium aluminum hydride, sodium, borohydride, diborane,etc. The reducing agent is usually used in an amount of at least onemole, preferably 1 to 10 moles, to 1 mole of the compound (1SS). Thereaction is usually carried out in an appropriate solvent, such aswater, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.),ethers (e.g. tetrahydrofuran, diethyl ether, diglyme, etc.), aceticacid, and the like, at a temperature of about 0° C. to about 200° C.,preferably about 0° C. to 170° C., for about 10 minutes to about 10hours. When lithium aluminum hydride or diborane is used as the reducingagent, it is preferable to use an anhydrous solvent such as diethylether, tetrahydrofuran, diglyme, etc. ##STR74## wherein R¹, R², R³, W',l, R^(14a) are as defined above, and R⁸³ is phenyl or a lower alkyl.

The reaction of the compound (1K) and the compound (63) can be carriedout under the same conditions as in the reaction of the compound (2b)and the compound (38) in the above Reaction Scheme-26. ##STR75## whereinR¹, R², R³, W', l, R^(14a) are as defined above.

The reaction of the compound (1K) and the glyconitrile (64) can becarried out in an appropriate solvent. The solvent includes the samesolvent as used in the reaction of the compound ( 7 ) and the compound (8 ) in the above Reaction Scheme-4. The reaction is usually carried outat a temperature of from about 0° C. to about 150° C., preferably about0° C. to about 100° C., for about 1 to 10 hours. The glyconitrile (64)is used in an amount of at least 1 mole, preferably 1 to 2 moles, to 1mole of the compound (1K). ##STR76## wherein R¹, R², R³, W', l, R^(14a)are as defined above, R⁸⁴ is a lower alkoxycarbonyl-substituted loweralkyl, R⁸⁵ is an amino having optionally a lower alkyl substituent, R⁸⁶is an aminocarbonyl-lower alkyl having optionally a lower alkylsubstituent, and R⁸⁷ is a carboxy-substituted lower alkyl.

The reaction of the compound (iVV) and the compound (65) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1.

The hydrolysis reaction of the compound (1VV) can be carried out underthe same conditions as in the hydrolysis reaction of the compound (1QQ)and the compound (62) in the above Reaction Scheme-41. ##STR77## whereinR¹, R², R³, W', X, and R^(14a) are as defined above, R⁸⁸ is atetrahydropyranyloxy-substituted lower alkyl, R⁸⁹ is a loweralkanoyloxy-substituted lower alkyl, R⁹⁰ is a hydroxy-substituted loweralkyl, and R⁹¹ is a lower alkanoyl.

The reaction of the compound (1YY) and the compound (66) can be carriedout in a solvent such as acetic acid at a temperature of about 0° C. toabout 200° C., preferably about 0° C. to about 150° C. for about 0 5 to15 hours

The hydrolysis reaction of the compound (1YY) can be carried out underthe same conditions as in the hydrolysis reaction of the compound (1QQ)and the compound (62) in the above Reaction Scheme-41, wherein apyridinium salt (e.g. pyridinium p-toluenesulfonate, etc.) may be usedas the acid. ##STR78## wherein R¹, R², R³, W', and R²⁶ are as definedabove.

The reaction of converting the compound (1A) into the compound (1bbb)can be carried out under the same conditions as in the reaction ofconverting the compound (1A) into the compound (1C) in the aboveReaction Scheme-15. ##STR79## wherein R¹, R², R³ and W' are as definedabove, R⁹² and R⁹³ are each a lower alkoxy.

The reaction of the compound (1ll) and the compound (68) is carried outin an appropriate solvent in the presence of an acid. The solventincludes, for example, water, alcohols (e.g. methanol, ethanol,isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.),ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether,etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixtureof these solvents. The acid includes, for example, mineral acids (e.g.hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids(e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.). Thereaction is usually carried out at a temperature of from roomtemperature to about 200° C., preferably from room temperature to about150° C., for about 0.5 to 5 hours. The compound (68) is usually used inan amount of at least 1 mole, preferably 1 to 2 moles, to 1 mole of thecompound (1ll). ##STR80## wherein R¹, R², R³, W', and R^(14a) are asdefined above, R⁹⁴ is a halogen-substituted lower alkanoyl, R⁹⁵ is animidazolyl-substituted lower alkanoyl or an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl, and R⁹⁶ is imidazolyl, or an amino having optionally asubstituent selected from a lower alkyl and a lower alkoxycarbonyl.

The reaction of the compound (1ddd) and the compound (69) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR81## wherein R¹,R², R³, and W' are as defined above, R⁹⁷ is a lower alkanoyloxy having ahalogen substituent, R⁹⁸ is an amino having optionally a lower alkylsubstituent, and R⁹⁹ is an amino-lower alkanoyloxy having optionally alower alkyl substituent.

The reaction of the compound (1fff) and the compound (70) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR82## wherein R¹,R², R³, W', R⁸², and R⁸³ are as defined above, R¹⁰⁰ is acarboxy-substituted lower alkoxy, and R¹⁰¹ is a group of the formula:##STR83## (A, R⁸² and R⁸³ are as defined above).

The reaction of the compound (1hhh) and the compound (71) can be carriedout under the same conditions as in the reaction of the compound (2) andthe compound (3) in the above Reaction Scheme-1. ##STR84## wherein R¹,R², R³, W", X, and R⁸² are as defined above, and R¹⁰² is hydrogen atomor a lower alkyl, provided that in the compound (1jjj), the groups ofthe formulae: --NH--R¹⁰² and --OH are substituted at the positionsadjacent each other.

The reaction of the compound (1jjj) and the compound (72) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction Scheme-4. ##STR85## wherein R¹,R², R³, W', R²⁶ and X are as defined above, and R¹⁰⁴ is a lower alkyl.

The reaction of the compound (1A) and the compound (73) can be carriedout in an appropriate solvent. The solvent includes, for example, ethers(diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons(e.g. benzene, toluene, xylene, etc.), saturated hydrocarbons (e.g.pentane, hexane, heptane, cyclohexane, etc.), or a mixture of thesesolvents. The reaction is usually carried out at a temperature of fromabout -70° C. to about 50° C. preferably from about -30° C. to roomtemperature, for about 1 to 6 hours. The compound (73) is used in anamount of at least 1 mole, preferably 1 to 5 moles, to 1 mole of thecompound (1A). ##STR86## wherein R¹, R², R³, W', R^(58'), R^(59'), and Aare as defined above, and R¹⁰⁵ is a lower alkylsulfonyloxy.

The reaction of the compound (1mmm) and the compound (74) can be carriedout under the same conditions as in the reaction of the compound (7) andthe compound (8) in the above Reaction° Scheme-4.

Among the active compounds (1) of this invention, the compounds havingan acidic group can easily be converted into salts by treating with apharmaceutically acceptable basic compound. The basic compound includes,for example, metal hydroxides such as sodium hydroxide, potassiumhydroxide, lithium hydroxide, calcium hydroxide, etc., alkali metalcarbonates or hydrogen carbonates such as sodium carbonate, sodiumhydrogen carbonate, etc., alkali metal alcoholates such as sodiummethylate, potassium ethylate, etc. Besides, among the active compounds(1) of this invention, the compounds having a basic group can easily beconverted into acid addition salts thereof by treating with apharmaceutically acceptable acid. The acid includes, for example,inorganic acids such as sulfuric acid,-nitric acid, hydrochloric acid,hydrobromic acid, etc., and organic acids such as acetic acid,p-toluene-sulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid,fumaric acid, citric acid, succinic acid, benzoic acid, etc. These saltsare useful as an active ingredient as like as the compounds (1) in thefree form.

In addition, the compounds (1) of this invention include stereoisomersand optical isomers, and these isomers are also useful as the activeingredient in this invention.

The compounds of this invention thus obtained can easily be isolated andpurified by conventional isolation methods. The isolation methods are,for example, distillation method, recrystallization method, columnchromatography, ion exchange chromatography, gel chromatography,affinity chromtography, preparative thin layer chromatography,extraction with a solvent, and the like.

The compounds and their salts of this invention are useful as avasopressin antagonist and are used in the form of a conventionalpharmaceutical preparation. The preparation is prepared by usingconventional dilutents or carriers such as fillers, thickening agents,binders, wetting agents, disintegrators, surfactants, lubricants, andthe like. The pharmaceutical preparations may be selected from variousforms in accordance with the desired utilities, and the representativeforms are tablets, pills, powders, solutions, suspensions, emulsions,granules, capsules, suppositories, injections (solutions, suspensions,etc.), and the like. In order to form in tablets, there are usedcarriers such as vehicles (e.g. lactose, white sugar, sodium chloride,glucose, urea, starches, calcium carbonate, kaolin, crystallinecellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol,simple syrup, glucose solution, starch solution, gelatin solution,carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate,polyvinylpyrrolidone, etc.), disintegrators (e.g. dry starch, sodiumarginate, agar powder, laminaran powder, sodium hydrogen carbonate,calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodiumlaurylsulfate, stearic monoglyceride, starches, lactose, etc.),disintegration inhibitors (e.g. white sugar, stearin, cacao butter,hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammoniumbase, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin,starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonire,colloidal silicates, etc.), lubricants (e.g. purified talc, stearates,boric acid powder, polyethylene glycol, etc.), and the like. Moreover,the tablets may also be in the form of a conventional coated tablet,such as sugar-coated tablets, gelatin-coated tablets, enteric coatedtablets, film coating tablets, or double or multiple layer tablets. Inthe preparation of pills, the carriers include vehicles (e.g. glucose,lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin,talc, etc.), binders (e.g. gum arabic powder, tragacanth powder,gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.),and the like. In the preparation of suppositories, the carriers include,for example, polyethylene glycol, cacao butter, higher alcohols, higheralcohol esters, gelatin, semi-synthetic glycerides, and the like.Capsules can be prepared by charging a mixture of the compound of thisinvention with the above carriers into hard gelatin capsules or softcapsules in a usual manner. In the preparation of injections, thesolutions, emulsions or suspendions are sterilized and are preferablymade isotonic with the blood. In the preparation of these solutions,emulsions and suspensions, there are used conventional diluents, such aswater, ethyl alcohol, macrogol (propylene glycol), ethoxylatedisostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylenesorbitan fatty acid esters, and the like. In this case, thepharmaceutical preparations may also be incorporated with sodiumchloride, glucose, or glycerin in an amount sufficient to make themisotonic, and may also be incorporated with conventional solubilizers,buffers, anesthetizing agents. Besides, the pharmaceutical preparationsmay optionally be incorporated with coloring agents, preservatives,perfumes, flavors, sweeting agents, and other medicaments, if required.

The amount of the active compound of this invention (active ingredient)to be incorporated into the anti-vasopressin preparations is notspecified but may be selected from a broad range, but usually, it ispreferably in the range of 1 to 70% by weight, more preferably 5 to 50%by weight.

The anti-vasopressin preparation of this invention may be administeredin any method, and suitable method for administration may be determinedin accordance with various forms of preparation, ages, sexes and otherconditions of the patients, the degree of severity of diseases, and thelike. For instance, tablets, pills, solutions, suspensions, emulsions,granules and capsules are administered orally. The injections areintraveneously administered alone or together with a conventionalauxiliary liquid (e.g. glucose, amino acid solutions), and further areoptionally administered alone in intramuscular, intracutaneous,subcutaneous, or intraperitoneal route, if required. Suppositories areadministered in intrarectal route.

The dosage of the anti-vasopressin agent of this invention may beselected in accordance with the usage, ages, sexes and other conditionsof the patients, the degree of severity of the diseases, and the like,but is usually in the range of about 0.6 to 50 mg of the active compoundof this invention per 1 kg of body weight of the patient per day. Theactive compound is preferably contained in an amount of 10 to 1000 mgper the dosage unit.

BRIEF DESCRIPTION OF DRAWING

FIG. 1 to FIG. 4 show a chart of NMR (CDCl₃) of the compounds inExamples 978 and 979.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is illustrated by the following Preparations ofanti-vasopressin agent, Reference Examples of processes for preparingthe starting compounds to be used for preparing the active compounds,Examples of processes for preparing the active compounds, andExperiments of the activities of the active compounds of this invention.

PREPARATION 1

Film coated tablets are prepared from the following components.

    ______________________________________                                        Components               Amount                                               ______________________________________                                        4-Methylamino-1-[4-(3,5-dichlorobenzoyl-                                                               150 g                                                amino)benzoyl]-1,2,3,4-tetrahydroquinoline                                    Avicel (tradename of microcrystalline cellulose,                                                       40 g                                                 manufactured by Asahi Chemical Industry                                       Co., Ltd., Japan)                                                             Corn starch              30 g                                                 Magnesium stearate        2 g                                                 Hydroxypropyl methylcellulose                                                                          10 g                                                 Polyethylene glycol-6000  3 g                                                 Castor oil               40 g                                                 Ethanol                  40 g                                                 ______________________________________                                    

The active component of this invention, Avicel, corn starch andmagnesium stearate are mixed and kneaded and the mixture is tablettedusing a conventional pounder (R 10 mm) for sugar coating. The tabletsthus obtained are coated with a film coating agent consisting ofhydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil andethanol to give film coated tablets.

PREPARATION 2

Tablets are prepared from the following components.

    ______________________________________                                        Components              Amount                                                ______________________________________                                        1-[4-(N-Butylanilinoacetylamino)benzoyl]-                                                              150 g                                                2,3,4,5-tetrahydroy-1H-benzazepine                                            Citric acid              1.0 g                                                Lactose                 33.5 g                                                Dicalcium phosphate     70.0 g                                                Pullonic F-68           30.0 g                                                Sodium laurylsulfate    15.0 g                                                Polyvinylpyrrolidone    15.0 g                                                Polyethylene glycol (Carbowax 1500)                                                                    4.5 g                                                Polyethylene glycol (Carbowax 6000)                                                                   45.0 g                                                Corn starch             30.0 g                                                Dry sodium stearate      3.0 g                                                Dry magnesium stearate   3.0 g                                                Ethanol                 q.s.                                                  ______________________________________                                    

The active compound of this invention, citric acid, lactose, dicalciumphosphate, Pullonic F-68 and sodium laurylstearate are mixed. Themixture is screened with No. 60 screen and is granulated with an alcoholsolution containing polyvinylpyrrolidone, carbowax 1500 and 6000. Ifrequired, an alcohol is added thereto so that the powder mixture is madea paste-like mass. Corn starch is added to the mixture and the mixtureis continuously mixed to form uniform particles. The resulting particlesare passed through No. 10 screen and entered into a tray and then driedin an oven at 100° C. for 12 to 14 hours. The dried particles arescreened with No. 16 screen and thereto are added dry sodiumlaurylsulfate and dry magnesium stearate, and the mixture is tablettedto form the desired shape.

The core tablets thus prepared are vanished and dusted with talc inorder to guard from wetting. Undercoating is applied to the coretablets. In order to administer the tablets orally, the core tablets arevanished several times. In order to give round shape and smooth surfaceto the tablets, further undercoating and coating with lubricant areapplied thereto. The tablets are further coated with a coloring coatingmaterial until the desired colored tablets are obtained. After drying,the coated tablets are polished to obtain the desired tablets havinguniform gloss.

PREPARATION 3

An injection preparation is prepared from the following components.

    ______________________________________                                        Components                 Amount                                             ______________________________________                                        4-Methyl-1-[4-(2,3-dimethylbenzoyl-                                                                      5      g                                           amino)benzoyl]-2,3,4,5-tetrahydro-                                            1H-1,4-benzodiazepine                                                         Polyethylene glycol (molecular weight: 4000)                                                             0.3    g                                           Sodium chloride            0.9    g                                           Polyoxyethylene sorbitan monooleate                                                                      0.4    g                                           Sodium metabisulfite       0.1    g                                           Methyl-paraben             0.18   g                                           Propyl-paraben             0.02   g                                           Distilled water for injection                                                                            10.0   ml                                          ______________________________________                                    

The above parabens, sodium metabisulfite and sodium chloride aredissolved in distilled water of half volume of the above with stirringat 80° C. The solution thus obtained is cooled to 40° C., and the activecompound of this invention and further polyethylene glycol andpolyoxyethylene sorbitan monooleate are dissolved in the above solution.To the solution is added distilled water for injection to adjust to thedesired volume, and the solution is sterilized by filtering with anappropriate filter paper to give an injection preparation.

REFERENCE EXAMPLE 1

To a solution of 1,2,3,4-tetrahydroquinoline (28.7 g) in acetone (400ml) and water (200 ml) is added potassium carbonate (38.8 g), andthereto is added p-nitrobenzoyl chloride (40 g) under ice-cooling andthe mixture is stirred at room temperature overnight. To the reactionmixture is added a suitable amount of water. The precipitated crystal iscollected by filtration and dried to give1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline (40.8 g) as white powder,m.p. 86°-88° C.

REFERENCE EXAMPLE 2

To a solution of 10% Pd-C (5 g) in ethanol (500 ml) is added1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline (53.4 g) and the mixtureis subjected to catalytic reduction at ordinary temperature underatmospheric pressure of hydrogen. After the reduction, 10% Pd-C isremoved by filtration, and the filtrate is concentrated under reducedpressure to give 1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline (46.7 g)as yellow powder, m.p. 185°-188° C.

REFERENCE EXAMPLE 3

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

1-(3-Nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, white powder, m.p.134°-136° C.

1-(2-Nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder, m.p.152°-154° C.

3-Methyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 109°-110° C.

4-Methyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 134°-136° C.

2-Methyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 143°-145° C.

1-(4-Nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellow powder,m.p. 143°-145° C.

1-(3-Methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 100°-102° C.

1-(3-Methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellowpowder, m.p. 146°-148° C.

1-(4-Nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, white powder, m.p.83°-85° C.

1-(4-Nitrobenzoyl)-3,4-dihydro-2H-1,4-benzoxazine, yellow powder, m.p.167°-169° C.

1-(4-Nitrobenzoyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine, yellow powder,m.p. 196°-198° C.

1-(4-Nitrobenzoyl)-4-methyl-1,2,3,4-tetrahydroquinoxaline, brown powder

1H-NMR (CDCl₃) δ: 3.03 (3H, s), 3.54 (2H, t, J=5.7 Hz), 4.06 (2H, t,J=5.7 Hz), 6.2-6.5 (2H, m), 6.70 (1H, d, J=8.2 Hz), 6.9-7.1 (1H, m),7.54 (2H, d, J=8.8 Hz), 8.13 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.7-2.0 (1H, m), 2.0-2.3 (1H, m), 2.8-3.0 (1H, m),2.98 (3H, s), 3.0-3.2 (1H, m), 3.4-3.6 (1H, m), 4.6-4.8 (1H, m), 6.5-6.7(2H, m), 6.94 (1H, d, J=8.1 Hz), 7.1-7.2 (1H, m), 7.33 (2H, d, J=8.9Hz), 7.97 (2H, d, J=8.9 Hz)

1-(4-Nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,brown oil

¹ H-NMR (CDCl₃) δ: 2.44 (3H, s), 3.0-3.3 (3H, m), 3.77 (1H, d, J=13.7Hz), 4.06 (1H, d, J=13.6 Hz), 4.9-5.1 (1H, m), 6.59 (1H, d, J=7.7 Hz),6.97 (1H, t, J=7.6 Hz), 7.15 (1H, t, J=7.4 Hz), 7.2-7.5 (3H, m), 8.03(2H, d, J=8.8 Hz)

1-(3-Methoxy-4-nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 146°-148° C.

1-(4-Nitrobenzoyl)-4-n-propyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 131°-133° C.

1-(4-Nitrobenzoyl)-5-chloro-1,2,3,4-tetrahydroquinoline, white powder,m.p. 134°-136° C.

1-(4-Nitrobenzoyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 149°-151° C.

1-(4-Nitrobenzoyl)-6-methyl-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 109°-110° C.

1-(4-Nitrobenzoyl)-7-methoxy-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 139°-141° C.

1-(4-Nitrobenzoyl)-3-(4-methyl-1-piperazinyl)-1,2,3,4-tetrahydroquinoline,yellow amorphous

¹ H-NMR (CDCl₃) δ: 2.29 (3H, s), 2.35-3.20 (11H, m), 3.86-4.15 (2H, m),6.48-6.63 (1H, m), 6.89 (1H, t, J=7.4 Hz), 7.05 (1H, t, J=7.4 Hz), 7.22(1H, d, J=7.4 Hz), 7.52 (2H, d, J=8.8 Hz), 8.11 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-3-(1-pyrrolidinyl)-1,2,3,4-tetrahydroquinoline,yellow amorphous

¹ H-NMR (CDCl₃) δ: 1.70-1.95 (4H, m), 2.52-3.30 (7H, m), 3.80-4.22 (2H,m), 6.52 (1H, brs), 6.88 (1H, t, J=7.6 Hz), 6.96-7.11 (1H, m), 7.20 (2H,d, J=7.6 Hz), 7.54 (2H, d, J=8.8 Hz), 8.12 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-4-oxo-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 189°-190° C.

1-(4-Nitrobenzoyl)-3-hydroxymethyl-1,2,3,4-tetrahydroquinoline, yellowpowder, m.p. 97°-100° C.

1-(4-Nitrobenzoyl)-3-ethoxycarbonyl-1,2,3,4-tetrahydroquinoline, paleyellow powder, m.p. 162°-163° C.

1-(4-Nitrobenzoyl)-4-dimethylamino-1,2,3,4-tetrahydroquinoline, lightbrown oil

¹ H-NMR (CDCl₃) δ: 1.80-2.02 (1H, m), 2.20-2.50 (7H, m), 3.47 (1H, t,J=4.9 Hz), 3.70-3.88 (1H, m), 4.06-4.25 (1H, m), 6.46 (1H, d, J=7.5 Hz),6.89 (1H, t, J=7.5 Hz), 7.05 (1H, t, J=7.5 Hz), 7.34 (1H, d, J=7.5 Hz),7.50 (2H, d, J=7.0 Hz), 8.10 (2H, d, J=7.0 Hz)

REFERENCE EXAMPLE 4

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

1-(3-Aminobenzoyl)-1,2,3,4-tetrahydroquinoline, white powder, m.p.128°-130° C.

1-(2-Aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder

¹ H-NMR (CDCl₃)δ: 2.01 (2H, quint, J=6.6 Hz), 2.81 (2H, t, J=6.6 Hz),3.86 (2H, t, J=6.4 Hz), 4.6-4.8 (2H, m), 6.43 (1H, t, J=7 Hz), 6.66 (1H,d, J=8 Hz), 6.79 (1H, dd, J=1.4 Hz, J=7.6 Hz), 6.8-7.2 (5H, m)

3-Methyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 197°-200° C.

4-Methyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 197°-199° C.

2-Methyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow powder,m.p. 204°-206° C.

1-(4-Aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellow powder,m.p. 172°-174° C.

1-(3-Methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 156°-158° C.

1-(3-Methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 165°-167° C.

1-(4-Aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, white powder, m.p.177°-179° C.

1-(4-Aminobenzoyl)-3,4-dihydro-2H-1,4-benzoxazine, white powder, m.p.192°-194° C.

1-(4-Aminobenzoyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine, yellow powder,m.p. 196°-198° C.

1-(4-Aminobenzoyl)-4-methyl-1,2,3,4-tetrahydroquinoxaline, yellowpowder, m.p. 210°-212° C.

1-(4-Aminobenzoyl)-5-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine,white powder, m.p. 159°-161° C.

1-(4-Aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,brown powder, m.p. 169°-171° C.

1-(3-Methoxy-4-aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 2.41 (3H, s), 2.9-3.2 (3H, m), 3.61 (3H, s), 3.6-4.2(4H, m), 4.8-5.2 (1H, m), 6.38 (1H, d, J=8.1 Hz), 6.6-6.8 (3H, m),6.9-7.2 (2H, m), 7.2-7.4 (1H, m)

1-(4-Aminobenzoyl)-4-n-propyl-2,3,4,5-tetrahydro-1H-1,4-benzazepine,brown powder, m.p. 151°-153° C.

1-(4-Aminobenzoyl)-5-chloro-1,2,3,4-tetrahydroquinoline, white powder,m.p. 174°-175° C.

1-(4-Aminobenzoyl)-6-methoxy-1,2,3,4-tetrahydroquinoline, pale yellowpowder, m.p. 159°-160° C.

1-(4-Aminobenzoyl)-6-methyl-1,2,3,4-tetrahydroquinoline, white powder,m.p. 145°-146° C.

1-(4-Aminobenzoyl)-7-methoxy-1,2,3,4-tetrahydroquinoline, pale yellowpowder, m.p. 150°-152° C.

1-(4-Aminobenzoyl)-3-(4-methyl-1-piperazinyl)-1,2,3,4-tetrahydroquinoline,light beige powder, m.p. 157°-159° C.

1-(4-Aminobenzoyl)-3-(1-pyrrolidinyl)-1,2,3,4-tetrahydroquinoline, paleyellow powder, m.p. 173°-174.5° C.

1-(4-Aminobenzoyl)-2,3-dihydro-4(1H)-quinolinone, pale yellow powder,m.p. 178°-180° C.

1-(4-Aminobenzoyl)-3-hydroxymethyl-1,2,3,4-tetrahydroquinoline, whitepowder, m.p. 179°-181° C.

1-(4-Aminobenzoyl)-3-ethoxycarbonyl-1,2,3,4-tetrahydroquinoline, paleyellow amorphous

¹ H-NMR (CDCl₃) δ: 1.21 (3H, t, J=7.1 Hz), 3.00-3.24 (3H, m), 3.70-4.30(6H, m), 6.48 (2H, d, J=8.5 Hz), 6.69 (1H, d, J=7.9 Hz), 6.77-7.30 (5H,m)

1-(4-Aminobenzoyl)-4-dimethylamino-1,2,3,4-tetrahydroquinoline, brownoil

¹ H-NMR (CDCl₃) δ: 1.83-2.05 (1H, m), 2.13-2.30 (1H, m), 2.34 (6H, m),3.55-3.83 (2H, m), 3.89 (1H, brs), 3.97-4.18 (1H, m), 6.47 (2H, d, J=7.0Hz), 6.68 (1H, d, J=7.9 Hz), 6.85-7.05 (2H, m), 7.20 (2H, d, J=7.0 Hz) ,7.37 (1H, d, J=7.4 Hz)

REFERENCE EXAMPLE 5

To terephthalic acid monomethyl ester (15 g) is added thionyl chloride(100 ml) and the mixture is refluxed for 2 hours. The thionyl chlorideis distilled off under reduced pressure to give terephthalic acidchloride monomethyl ester. Separately, to a solution of1,2,3,4-tetrahydroquinoline (14.4 g) in dichloromethane (200 ml) isadded triethylamine (16.9 g) and further thereto is added slowlyterephthalic acid chloride monomethyl ester obtained above underice-cooling. Then, the mixture is stirred at room temperature for 1hour. After completion of the reaction, water is added to the reactionmixture. The mixture is extracted with dichloromethane and dried overmagnesium sulfate. The solvent is distilled off under reduced pressureand the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane) to give1-(4-methoxycarbonylbenzoyl)-1,2,3,4-tetrahydroquinoline (22.7 g) aswhite powder, m.p. 72°-74° C.

REFERENCE EXAMPLE 6

To a solution of1-(4-methoxycarbonylbenzoyl)-1,2,3,4-tetrahydroquinoline (22.7 g) inmethanol (300 ml) is added 5% aqueous sodium hydroxide solution (150 ml)and the mixture is refluxed for 2 hours. Methanol is distilled off underreduced pressure and the resulting residue is acidified with dilutedhydrochloric acid, extracted with diethyl ether, and dried overmagnesium sulfate. The solvent is distilled off under reduced pressureand the resulting crystal is collected by filtration to give1-(4-carboxybenzoyl)-1,2,3,4-tetrahydroquinoline (13.2 g) as whitepowder, m.p. 181°-183° C.

REFERENCE EXAMPLE 7

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-Dimethylamino-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,pale yellow powder, m.p. 139°-142° C.

5-Dimethylamino-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 139°-141° C.

4-(N-Methyl-N-ethylamino)-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline,pale yellow oil

¹ H-NMR (CDCl₃) δ: 1.11 (3H, t, J=7.1 Hz), 1.90-2.25 (2H, m), 2.30 (3H,s), 2.57 (2H, q, J=7.1 Hz), 3.55-3.85 (2H, m), 4.00-4.21 (1H, m),6.35-6.60 (1H, m), 6.80-6.98 (1H, t, J=7.9 Hz), 7.00-7.15 (1H, m),7.33-7.60 (3H, m), 8.10 (2H, d, J=8.8 Hz)

4-Dimethylamino-1-(3-methoxy-4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline,brown oil

¹ H-NMR (CDCl₃) δ: 1.80-2.05 (1H, m), 2.33 (6H, s), 2.30-2.50 (1H, m),3.40-3.52 (1H, m), 3.78 (3H, s), 3.70-3.88 (1H, m), 4.04-4.24 (1H, m),6.52 (1H, d, J=8.2 Hz), 6.85-7.13 (4H, m), 7.28-7.38 (1H, m), 7.71 (1H,d, J=8.2 Hz)

1-(4-Nitrobenzoyl)-4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.16 (3H, t, J=7.1 Hz), 2.5-2.7 (2H, m), 3.0-3.3 (3H,m), 3.98 (2H, q, J=14 Hz), 4.8-5.0 (1H, m), 6.59 (1H, d, J=7.7 Hz), 6.96(1H, t, J=7.7 Hz), 7.14 (1H, t, J=7.4 Hz), 7.2-7.4 (3H, m), 8.02 (2H, d,J=8.8 Hz)

1-(4-Nitrobenzoyl)-4-isopropyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 222°-223° C.

1-(4-Nitrobenzoyl)-4-cyclohexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,brown oil

¹ H-NMR (CDCl₃) δ: 1.0-1.5 (5H, m), 1.5-2.1 (5H, m), 2.4-2.7 (1H, m),2.9-3.3 (3H, m), 3.94 (2H, s), 4.9-5.1 (1H, m), 6.57 (1H, d, J=7.7 Hz),6.8-7.0 (1H, m), 7.0-7.2 (1H, 7.2-7.4 (3H, m), 8.01 (2H, d, J=8.8 Hz)

1-(4-Nitrobenzoyl)-5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-2.1 (2H, m), 2.40 (3H, s), 2.3-2.6 (1H, m),2.8-3.2 (2H, m), 3.50 (1H, d, J=13.4 Hz), 3.84 (1H, d, J=13.4 Hz),4.8-5.0 (1H, m), 7.0-7.3 (4H, m), 7.41 (2H, d, J=8.9 Hz), 8.00 (2H, d,J=8.9 Hz)

1-(4-Nitrobenzoyl)-1,2,3,4-tetrahydro-5,1-benzoxazepine, white powder,m.p. 144.5°-145.5° C.

1-(2-Nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 177°-180° C.

1-(3-Nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 145°-146° C.

6-Fluoro-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline, yellow needles,m.p. 145°-146° C.

REFERENCE EXAMPLE 8

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-Dimethylamino-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 120°-122° C.

5-Dimethylamino-1-(3-methoxy-4-amino)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 121°-123° C.

4-(N-Methy-N-ethylamino)-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline,orange amorphous

¹ H-NMR (CDCl₃) δ: 1.11 (3H, t, J=7.1 Hz), 1.90-2.20 (2H, m), 2.28 (3H,s), 2.26 (2H, q, J=7.1 Hz), 3.60-4.25 (5H, m), 6.48 (2H, d, J=8.5 Hz),6.69 (1H, d, J=7.9 Hz), 6.80-7.05 (2H, m), 7.24 (2H, d, J=8.5 Hz), 7.46(1H, d, J=6.2 Hz)

4-Dimethylamino-1-(3-methoxy-4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline,pale yellow amorphous

¹ H-NMR (CDCl₃) δ: 1.83-2.04 (1H, m), 2.15-2.32 (1H, m), 2.33 (6H, s),3.50-3.82 (2H, m), 3.64 (3H, s), 3.95-4.18 (3H, m), 6.50 (1H, d, J=7.9Hz), 6.65 (1H, dd, J=7.9 Hz, 1.1 Hz), 6.78-7.03 (4H, m), 7.34 (1H, dd,J=7.5 Hz, 1.5 Hz)

1-(4-Aminobenzoyl)-4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 186°-188° C.

1-(4-Aminobenzoyl)-4-isopropyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 191°-192° C.

1-(4-Aminobenzoyl)-4-cyclohexyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 149.5°-150.5° C.

1-(4-Aminobenzoyl)-5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocine,yellow powder, m.p. 143°-145° C.

1-(4-Aminobenzoyl)-1,2,3,4-tetrahydro-5,1-benzoxazepine, yellow powder,m.p. 163.5°-164.5° C.

1-(2-Aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,yellow powder, m.p. 144°-146° C.

1-(3-Aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, mp. 153°-155° C.

6-Fluoro-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline, white powder,m.p. 160.5°-161.5° C.

REFERENCE EXAMPLE 9

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

1-(2-Chloro-4-nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

¹ H-NMR (CDCl₃) δ: 2.40 (3H, s), 2.96-3.33 (3H, m), 3.60-3.79 (1H, m),3.96-4.23 (1H, m), 4.70-4.91 (1H, m), 6.80-7.43 (5H, m), 7.80-7.99 (1H,m), 8.08-8.21 (1H, m)

1-(3-Methyl-4-nitrobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

¹ H-NMR (CDCl₃) δ: 2.43 (3H, s), 2.48 (3H, s), 2.92-3.28 (3H, m), 3.91(2H, AB-q, J=13.9 Hz, 45.5 Hz), 4.77-5.01 (1H, m), 6.54-6.70 (1H, m),6.88-7.37 (5H, m), 7.62-7.78 (1H, m)

5-Dimethylamino-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

¹ H-NMR (CDCl₃) δ: 1.23-2.57 (10H, m), 2.68-5.15 (3H, m), 6.79-7.45 (4H,m), 7.49-8.39 (3H, m)

5-Oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, white powder(ethyl acetate/n-hexane), m.p. 147°-148° C.

5-Hydroxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder (ethyl acetate/n-hexane), m.p. 148°-150° C.

5-Methoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.47-2.48 (4H, m), 2.70-3.10 (1H, m), 3.26-3.64 (3H,m), 4.29-5.12 (2H, m), 6.60 (1H, d, J=7.7 Hz), 6.88-7.67 (5H, m),7.92-8.12 (2H, m)

5-Ethoxycarbonylmethoxyl-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 107°-108° C. (recrystallized from ethylacetate/n-hexane)

5-(4-Bromobutoxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless oil

¹ H-NMR (CDCl₃) δ: 1.49-2.55 (5H, m), 2.72-3.07 (1H, m), 3.24-3.77 (4H,m), 4.40-5.15 (2H, m), 6.53-6.66 (1H, m) , 6.91-7.06 (1H, m), 7.07-7.80(4H, m), 7.94-8.13 (2H, m)

5-(4-Dimethylaminobutoxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless oil

¹ H-NMR (CDCl₃) δ: 1.51-1.88 (6H, m), 2.23-2.61 (4H, m), 2.27 (3H, s),2.35 (3H, s), 2.74-3.14 (1H, m), 3.55-3.77 (2H, m), 4.48-5.11 (2H, m),6.54-6.66 (1H, m), 6.91-7.04 (1H, m), 7.06-7.80 (4H, m), 7.93-8.11 (2H,m)

5-[4-(Phthalimid-1-yl)propoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.48-2.56 (6H, m), 2.71-3.05 (1H, m), 3.40-4.05 (4H,m), 4.47-5.11 (2H, m), 6.50-6.64 (1H, m), 6.84-7.03 (1H, m), 7.03-7.20(1H, m), 7.20-7.57 (2H, m), 7.57-7.93 (5H, m), 7.97-8.20 (2H, m)

5-Chloro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, lightbrown powder

¹ H-NMR (CDCl₃) δ: 1.75-3.3 (4H, m), 4.6-6.25 (3H, m), 6.45-6.7 (1H, m),6.8-7.5 (4H, m), 7.55-7.7 (1H, m), 7.9-8.1 (2H, m)

5-Oxo-1-(2-chloro-4-nitorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,pale yellow amorphous

¹ H-NMR (CDCl₃) δ: 1.95-2.45 (2H, m), 2.94 (1H, t, J=6 Hz), 3.05-5.3(2H, m), 6.96-7.1 (1H, m), 7.12-7.5 (3H, m), 7.75-7.85 (1H, m), 7.95-8.1(1H, m), 8.14 (1H, s)

4-Dimethylaminomethyl-1-(4-nitrobenzoyl)-1,2,3,4-tetrahydroquinoline,white powder, m.p. 117°-119° C.

3-Dimethylamino-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-1.7 (1H, m), 2.1-2.4 (1H, m), 2.42 (6H, s),2.6-2.7 (1H, m), 2.8-3.0 (3H, m), 5.1-5.3 (1H, m), 6.62 (1H, d, J=7.8Hz), 6.95 (1H, t, J=7.7 Hz), 7.14 (1H, t, J=7.5 Hz), 7.2-7.4 (3H, m),8.00 (2H, d, J=8.9 Hz)

3-Dimethylamino-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-1.7 (1H, m), 2.0-2.3 (1H, m), 2.41 (6H, s),2.5-2.8 (1H, m), 2.8-3.0 (3H, m), 3.75 (3H, s), 5.1-5.3 (1H, m), 6.6-6.8(2H, m), 6.9-7.3 (4H, m), 7.59 (1H, d, J=8.3 Hz)

4-(4-Nitrobenzoyl)-3,4-dihydro-2H-1,4-benzothiazine, yellow powder, m.p.180°-182° C.

5-(4-Nitrobenzoyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine, yellowpowder, m.p. 162°-163° C.

REFERENCE EXAMPLE 10

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

1-(2-Chloro-4-aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder (recrystallized from methanol/diethyl ether), m.p.194.5°-195.5° C.

1-(3-Methyl-4-aminobenzoyl)-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

¹ H-NMR (CDCl₃) δ: 2.01 (3H, s), 2.41 (3H, s), 2.82-3.21 (3H, m),3.50-4.21 (4H, m), 4.78-5.14 (1H, m), 6.24-6.40 (1H, m), 6.59-6.82 (2H,m), 6.90-7.18 (3H, m), 7.19-7.34 (1H, m)

5-Dimethylamino-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether), m.p.162°-164° C.

5-Dimethylamino-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(recrystallized from methanol/diethyl ether)

¹ H-NMR (CDCl₃) δ: 1.23-2.80 (11H, m), 2.90-3.38 (1H, m) , 3.50-5.19(6H, m), 5.87-6.41 (2H, m), 6.65-7.56 (5H, m)

5-Methoxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder (recrystallized from ethyl acetate/n-hexane), m.p. 154°-155° C.

5-Ethoxycarbonylmethoxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from ethyl acetate/n-hexane), m.p.231°-232° C.

5-(4-Dimethylaminobutoxy)-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless oil

¹ H-NMR (CDCl₃) δ: 1.47-1.83 (6H, m), 1.83-2.54 (4H, m), 2.29 (6H, s),2.61-3.00 (1H, m), 3.36-3.76 (2H, m), 4.35-5.20 (2H, m), 6.27-6.48 (2H,m), 6.57-6.76 (1H, m), 6.90-7.61 (5H, m)

5-[4-(Phthalimid-1-yl)propoxy]-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.30-2.47 (6H, m), 2.57-3.01 (1H, m), 3.30-4.06 (4H,m), 4.34-5.20 (2H, m), 6.30-6.53 (2H, m) , 6.57-6.78 (1H, m), 6.87-7.57(5H, m), 7.62-7.76 (2H, m), 7.76-7.97 (2H, m)

5-Chloro-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, paleyellow amorphous

¹ H-NMR (CDCl₃) δ: 1.35-4.3 (7H, m), 4.55-6.7 (2H, m), 6.3-6.55 (2H, m),6.6-6.8 (1H, m), 6.85-7.45 (5H, m)

5-Oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, pale yellowamorphous

¹ H-NMR (CDCl₃) δ: 1.95-2.35 (2H, m), 2.89 (2H, t, J=6.3 Hz), 3.0-5.3(4H, m), 6.35-6.47 (2H, m), 6.72-6.83 (1H, m), 7.0-7.15 (2H, m),7.18-7.32 (2H, m), 7.81-7.93 (1H, m)

5-Oxo-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder

¹ H-NMR (CDCl₃) δ: 1.85-2.3 (2H, m), 2.87 (2H, t, J=6.2 Hz), 3.1-4.75(4H, m), 6.15-7.5 (6H, m), 7.65-7.9 (1H, m)

4-Dimethylaminomethyl-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline,white powder, m.p. 123°-125° C.

3-Dimethylamino-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 175°-177° C.

3-Dimethylamino-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.5-1.7 (1H, m), 2.1-2.3 (1H, m), 2.3-2.6 (1H, m),2.40 (6H, s), 2.7-3.0 (3H, m), 3.60 (3H, s), 3.8-4.0 (2H, br), 5.2-5.4(1H, m), 6.37 (1H, d, J=8.2 Hz), 6.5-6.8 (3H, m), 6.9-7.4 (3H, m)

4-(4-Aminobenzoyl)-3,4-dihydro-2H-1,4-benzothiazine, yellow powder, m.p.207°-210° C.

5-(4-Aminobenzoyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine, yellowpowder, m.p. 193°-195° C.

REFERENCE EXAMPLE 11

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-Carbamoyloxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 243°-244° C. (recrystallized from ethylacetate/diisopropyl ether)

5-Methylaminocarbonyloxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 207°-208° C. (recrystallized from ethylacetate/n-hexane)

5-Dimethylaminocarbonyloxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 155°-156° C. (recrystallized from ethylacetate/diisopropyl ether/n-hexane)

5-Methylidenyl-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless prisms, m.p. 133.5°-134° C. (recrystallized from ethylacetate/diisopropyl ether)

5-Oxo-6-methyl-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless prisms, m.p. 90°-92° C. (recrystallized from ethanol)

1-(4-Nitrobenzoyl)-1,2,3,5-tetrahydro-4,1-benzothiazepine, yellowpowder, m.p. 185°-187° C. (recrystallized from dichloromethane/diethylether)

5-Dimethylamino-1-(2-dimethylamino-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder, m.p. 123°-125° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine, whitepowder, m.p. 201.5°-202.5° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-4-methyl-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine,white powder, m.p. 136°-138° C. (recrystallized from diethylether/dichloromethane)

5-Dimethylamino-1-(3-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.16-3.18 (11H, m), 2.18 (3H, s), 3.40-5.15 (2H, m),6.50-7.68 (6H, m), 7.70-7.84 (1H, m)

5-Dimethylamino-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ: 1.19-2.86 (11H, m), 2.20 (3H, s), 2.94-3.24 (1H, m),3.36-5.18 (1H, m), 6.49-8.20 (7H, m)

5-Dimethylamino-1-(2-fluoro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 1.21-2.66 (10H, m), 2.66-5.11 (3H, m), 6.63-8.25 (7H,m)

5-Dimethylamino-1-(3-fluoro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 152°-152.5° C. (recrystallized fromchloroform/diethyl ether)

REFERENCE EXAMPLE 12

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-Carbamoyloxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 215°-216° C. (recrystallized from ethylacetate/n-hexane)

5-Methylaminocarbonyloxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 192°-195° C. (recrystallized from ethylacetate/n-hexane)

5-Dimethylaminocarbonyloxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 228°-230° C. (recrystallized from ethylacetate/diisopropyl ether)

5-Methyl-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, whitepowder, m.p. 155°-156° C. (recrystallized from ethyl acetate/n-hexane)

5-Oxo-6-methyl-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 193°-195° C. (recrystallized from ethanol)

1-(4-Aminobenzoyl)-1,2,3,5-tetrahydro-4,1-benzothiazepine, white powder,m.p. 179°-180° C. (recrystallized from dichloromethane/diethyl ether)

5-Dimethylamino-1-(2-dimethylamino-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 163°-165° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine, yellowpowder, m.p. 195°-197° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-4-methyl-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzazepine,yellow powder, m.p. 190°-192° C. (recrystallized from diethylether/dichloromethane)

5-Dimethylamino-1-(2-ethoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 111°-114° C. (recrystallized from diethyl ether)

5-Dimethylamino-1-(3-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ: 0.66-2.56 (14H, m), 2.93-5.22 (4H, m), 6.23-7.80 (7H,m)

5-Dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 154°-156° C. (recrystallized from methanol/diethylether)

5-Dimethylamino-1-(2-fluoro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 161°-163° C. (recrystallized fromdichloromethane/diethyl ether)

5-Dimethylamino-1-(3-fluoro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 156°-157° C. (recrystallized from methanol/diethylether)

5-Oxo-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless prisms, m.p. 160°-160.5° C. (recrystallized frommethanol/diethyl ether)

EXAMPLE 1

To a solution of 1,2,3,4-tetrahydroquinoline (28.7 g) in acetone (400ml) and water (200 ml) is added potassium carbonate (38.8 g) and furtherthereto is added 4-benzoylaminobenzoyl chloride (56 g) underice-cooling. The mixture is stirred at room temperature overnight. Wateris added to the reaction mixture, and the mixture is extracted withdichloromethane. The extract is dried over magnesium sulfate, and thesolvent is distilled off under reduced pressure. The resulting residueis purified by silica gel column chromatography and recrystallized frommethanol to give 1-[4-(benzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(57 g) as white powder, m.p. 202.5°-203.5° C.

Using the suitable starting materials, the compounds as shown in thefollowing Table 1 are obtained in the same manner as in Example 1.##STR87##

EXAMPLE 2 ##STR88## Crystalline form: Light yellow powderRecrystallization solvent: Methanol Melting Point: 198.5°-199.5° C.Form: Free EXAMPLE 3 ##STR89## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 200.5°-201.5° C.Form: Free EXAMPLE 4 ##STR90## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 206°-207° C. Form:Free EXAMPLE 5 ##STR91## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 216°-217° C. Form:Free EXAMPLE 6 ##STR92## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 202°-203° C. Form:Free EXAMPLE 7 ##STR93## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 212°-213° C. Form:Free EXAMPLE 8 ##STR94## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 167.5°-168.5° C.Form: Free EXAMPLE 9 ##STR95## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 205°-206° C. Form:Free EXAMPLE 10 ##STR96## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: >300° C. NMRanalysis: 1) Form: Free EXAMPLE 11 ##STR97## Crystalline form: Yellowpowder Recrystallization solvent: Methanol Melting Point: 176°-177° C.Form: Free EXAMPLE 12 ##STR98## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 219°-220° C. Form:Free EXAMPLE 13 ##STR99## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 193°-194° C. Form:Free EXAMPLE 14 ##STR100## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 232°-233° C. Form:Free EXAMPLE 15 ##STR101## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 209°-210° C. Form:Free EXAMPLE 16 ##STR102## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 184.5°-185.5° C.Form: Free EXAMPLE 17 ##STR103## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 224.5°-225.5° C.Form: Free EXAMPLE 18 ##STR104## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 220.5°-221.5° C.Form: Free EXAMPLE 19 ##STR105## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 231°-232° C. Form:Free EXAMPLE 20 ##STR106## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: >300° C. NMRanalysis: 2) Form: Free EXAMPLE 21 ##STR107## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 208°-209° C.Form: Free EXAMPLE 22 ##STR108## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 234.5°-235.5° C.Form: Free EXAMPLE 23 ##STR109## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 263.5°-264.5° C.Form: Free EXAMPLE 24 ##STR110## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 237°-238° C. Form:Free EXAMPLE 25 ##STR111## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 234°-235° C. Form:Free EXAMPLE 26 ##STR112## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 236.5°-237.5° C.Form: Free EXAMPLE 27 ##STR113## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 206.5°-207.5° C.Form: Free EXAMPLE 28 ##STR114## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 210°-211° C. Form:Free EXAMPLE 29 ##STR115## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 210.5°-211.5° C.Form: Free EXAMPLE 30 ##STR116## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 178°-179° C. Form:Free EXAMPLE 31 ##STR117## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 192°-193° C. Form:Free EXAMPLE 32 ##STR118## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 217°-218° C. Form:Free EXAMPLE 33 ##STR119## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 143°-144° C. Form:Free EXAMPLE 34 ##STR120## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 170.5°-171.5° C.Form: Free EXAMPLE 35 ##STR121## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 169.5°-170.5° C.Form: Free EXAMPLE 36 ##STR122## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 174.5°-175.5° C.Form: Free EXAMPLE 37 ##STR123## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 148.5°-149.5° C.Form: Free EXAMPLE 38 ##STR124## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 165°-166° C. Form:Free EXAMPLE 39 ##STR125## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 243°-244° C. Form:Free EXAMPLE 40 ##STR126## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 199°-200° C. Form:Free EXAMPLE 41 ##STR127## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 232.5°-233.5° C.Form: Free EXAMPLE 42 ##STR128## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 178.5°-179.5° C.Form: Free EXAMPLE 43 ##STR129## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 205.5°-206.5° C.Form: Free EXAMPLE 44 ##STR130## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 234°-235° C. Form:Free EXAMPLE 45 ##STR131## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 225°-226° C. Form:Free EXAMPLE 46 ##STR132## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 224°-225° C. Form:Free EXAMPLE 47 ##STR133## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 236°-237° C. Form:Free EXAMPLE 48 ##STR134## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 175.5°-176.5° C.Form: Free EXAMPLE 49 ##STR135## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 231°-232° C. Form:Free EXAMPLE 50 ##STR136## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 204°-205° C. Form:Free EXAMPLE 51 ##STR137## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 190°-191° C. Form:Free EXAMPLE 52 ##STR138## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 156°-157° C. Form:Free EXAMPLE 53 ##STR139## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 200°-201° C. Form:Free EXAMPLE 54 ##STR140## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 206°-207° C. Form:Free EXAMPLE 55 ##STR141## Crystalline form: Colorless amorphous NMRanalysis: 3) Form: Free EXAMPLE 56 ##STR142## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 215.5°-216.5°C. Form: Free EXAMPLE 57 ##STR143## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 189°-190° C. Form:Free EXAMPLE 58 ##STR144## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 203.5°-204.5° C.Form: Free EXAMPLE 59 ##STR145## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 254.5°-255.5° C.Form: Free EXAMPLE 60 ##STR146## Crystalline form: Brown powderRecrystallization solvent: Methanol Melting Point: 182.5°-183.5° C.Form: Free EXAMPLE 61 ##STR147## Crystalline form: Colorless amorphousNMR analysis: 4) Form: Free EXAMPLE 62 ##STR148## Crystalline form:White powder Recrystallization solvent: Methanol Melting Point:263°-264° C. Form: Free EXAMPLE 63 ##STR149## Crystalline form: Whitepowder Recrystallization solvent: Dichloromethane/ethanol Melting Point:217°-218° C. Form: Free EXAMPLE 64 ##STR150## Crystalline form: Whitepowder Recrystallization solvent: Dichloromethane/ethanol Melting Point:183°-184° C. Form: Free EXAMPLE 65 ##STR151## Crystalline form: Yellowpowder Recrystallization solvent: Dichloromethane/ethanol Melting Point:207.5°-208.5° C. Form: Free EXAMPLE 66 ##STR152## Crystalline form:Yellow powder Recrystallization solvent: Dichloromethane/ethanol MeltingPoint: 251°-252° C. Form: Free EXAMPLE 67 ##STR153## Crystalline form:White powder Recrystallization solvent: Dichloromethane/ethanol MeltingPoint: 208.5°-209.5° C. Form: Free EXAMPLE 68 ##STR154## Crystallineform: White powder Recrystallization solvent: Dichloromethane/ethanolMelting Point: 231°-232° C. Form: Free EXAMPLE 69 ##STR155## Crystallineform: Colorless amorphous NMR analysis: 5) Form: Free EXAMPLE 70##STR156## Crystalline form: White powder Recrystallization solvent:Methanol Melting Point: 134°-135° C. Form: Free EXAMPLE 71 ##STR157##Crystalline form: Yellow powder Recrystallization solvent: MethanolMelting Point: 115°-116° C. Form: Free EXAMPLE 72 ##STR158## Crystallineform: White powder Recrystallization solvent: Methanol Melting Point:178.5°-179.5° C. Form: Free EXAMPLE 73 ##STR159## Crystalline form:White powder Recrystallization solvent: Methanol Melting Point:182.5°-183.5° C. Form: Free EXAMPLE 74 ##STR160## Crystalline form:White powder Recrystallization solvent: Methanol Melting Point:164°-165° C. Form: Free EXAMPLE 75 ##STR161## Crystalline form:Colorless amorphous NMR analysis: 6) Form: Free EXAMPLE 76 ##STR162##Crystalline form: Yellow amorphous NMR analysis: 7) Form: Free EXAMPLE77 ##STR163## Crystalline form: White powder Recrystallization solvent:Methanol Melting Point: 155°-156° C. Form: Free EXAMPLE 78 ##STR164##Crystalline form: White powder Recrystallization solvent: MethanolMelting Point: 182.5°-183.5° C. Form: Free EXAMPLE 79 ##STR165##Crystalline form: White powder Recrystallization solvent: MethanolMelting Point: 164.5°-165.5° C. Form: Free EXAMPLE 80 ##STR166##Crystalline form: White powder Recrystallization solvent: MethanolMelting Point: 165°-167° C. Form: Free EXAMPLE 81 ##STR167## Crystallineform: White powder Recrystallization solvent: Methanol Melting Point:124°-125° C. Form: Free EXAMPLE 82 ##STR168## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 140.5°-141.5°C. Form: Free EXAMPLE 83 ##STR169## Crystalline form: Colorlessamorphous NMR analysis: 8) Form: Free EXAMPLE 84 ##STR170## Crystallineform: White powder Recrystallization solvent: Methanol Melting Point:211°-212° C. Form: Free EXAMPLE 85 ##STR171## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 178°-179° C.Form: Free EXAMPLE 86 ##STR172## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 212.5°-213.5° C.Form: Free EXAMPLE 87 ##STR173## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 193°-194° C. Form:Free EXAMPLE 88 ##STR174## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 203°-204° C. Form:Free EXAMPLE 89 ##STR175## Crystalline form: Colorless amorphous NMRanalysis: 9) Form: Free EXAMPLE 90 ##STR176## Crystalline form:Colorless amorphous NMR analysis: 10) Form: Free EXAMPLE 91 ##STR177##Crystalline form: Colorless amorphous NMR analysis: 11) Form: FreeEXAMPLE 92 ##STR178## Crystalline form: White powder Recrystallizationsolvent: Methanol Melting Point: 156.5°-157.5° C. Form: Free EXAMPLE 93##STR179## Crystalline form: Colorless amorphous NMR analysis: 12) Form:Free EXAMPLE 94 ##STR180## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 203.5°-204.5° C.Form: Free EXAMPLE 95 ##STR181## Crystalline form: Colorless amorphousNMR analysis: 13) Form: Free EXAMPLE 96 ##STR182## Crystalline form:Yellow powder Recrystallization solvent: Methanol Melting Point:126°-127° C. Form: Free EXAMPLE 97 ##STR183## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 158.5°-159.5°C. Form: Free EXAMPLE 98 ##STR184## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 129°-130° C. Form:Free EXAMPLE 99 ##STR185## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 131.5°-132.5° C.Form: Free EXAMPLE 100 ##STR186## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 140°-141° C. Form:Free EXAMPLE 101 ##STR187## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 138.5°-139.5° C.Form: Free EXAMPLE 102 ##STR188## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 128°-129° C. Form:Free EXAMPLE 103 ##STR189## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 160°-161° C. Form:Free EXAMPLE 104 ##STR190## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 175°-176° C. Form:Free EXAMPLE 105 ##STR191## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 197°-198° C. Form:Free EXAMPLE 106 ##STR192## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 204°-205° C. Form:Free EXAMPLE 107 ##STR193## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 174°-175° C. Form:Free EXAMPLE 108 ##STR194## Crystalline form: Yellow powderRecrystallization solvent: Methanol Melting Point: 202°-203° C. Form:Free EXAMPLE 109 ##STR195## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 203°-204° C. Form:Free EXAMPLE 110 ##STR196## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 170.5°-171.5° C.Form: Free EXAMPLE 111 ##STR197## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 149°-150° C. Form:Free EXAMPLE 112 ##STR198## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 185°-186° C. Form:Free EXAMPLE 113 ##STR199## Crystalline form: White powderRecrystallization solvent: Dichloromethane/ethanol Melting Point:225°-226° C. Form: Free EXAMPLE 114 ##STR200## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 234°-235° C.Form: Free EXAMPLE 115 ##STR201## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 149.5°-150.5° C.Form: Free EXAMPLE 116 ##STR202## Crystalline form: White powderRecrystallization solvent: Dichloromethane/ethanol Melting Point:197°-198° C. Form: Free EXAMPLE 117 ##STR203## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 204°-205° C.Form: Free EXAMPLE 118 ##STR204## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 224.5°-225. Form:Free EXAMPLE 119 ##STR205## Crystalline form: White powderRecrystallization solvent: Dichloromethane/ethanol Melting Point:189.5°-190.5° C. Form: Free EXAMPLE 120 ##STR206## Crystalline form:White powder Recrystallization solvent: Methanol Melting Point:221.5°-222.5° C. Form: Free EXAMPLE 121 ##STR207## Crystalline form:Colorless needles Recrystallization solvent: Methanol Melting Point:154°-155° C. Form: Free EXAMPLE 122 ##STR208## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 165°-166° C.Form: Free EXAMPLE 123 ##STR209## Crystalline form: Colorless needlesRecrystallization solvent: Methanol Melting Point: 141°-142° C. Form:Free EXAMPLE 124 ##STR210## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 165.5°-166.5° C.Form: Free EXAMPLE 125 ##STR211## Crystalline form: Colorless needlesRecrystallization solvent: Methanol Melting Point: 164°-165° C. Form:Free EXAMPLE 126 ##STR212## Crystalline form: White powderRecrystallization solvent: Methanol Melting Point: 203.5°-204.5° C.Form: Free EXAMPLE 127 ##STR213## Crystalline form: White powderRecrystallization solvent: Dichloromethane/ethanol Melting Point:236.5°-237.5° C. Form: Free EXAMPLE 128 ##STR214## Crystalline form:White powder Recrystallization solvent: Methanol Melting Point:206.5°-207.5° C. Form: Free EXAMPLE 129 ##STR215## Crystalline form:White powder Recrystallization solvent: Methanol Melting Point:271°-272° C. Form: Free EXAMPLE 130 ##STR216## Crystalline form: Whitepowder Recrystallization solvent: Methanol Melting Point: 246°-247° C.Form: Free EXAMPLE 131 ##STR217## Crystalline form: White powderRecrystallization solvent: Ethanol/diethyl ether Melting Point:210°-211° C. Form: Free EXAMPLE 132 ##STR218## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:230.5°-231.5° C. Form: Free EXAMPLE 133 ##STR219## Crystalline form:White powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 203°-204° C. Form: Free EXAMPLE 134 ##STR220## Crystalline form:White powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 170°-171° C. Form: Free EXAMPLE 135 ##STR221## Crystalline form:White powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 225.5°-226.5° C. Form: Free EXAMPLE 136 ##STR222## Crystallineform: White powder Recrystallization solvent: Ethanol/diethyl etherMelting Point: 210.5°-211.5° C. Form: Free EXAMPLE 137 ##STR223##Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 183°-184° C. Form: Free EXAMPLE 138##STR224## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 191.5°-192.5° C. Form: Free EXAMPLE139 ##STR225## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 203.5°-204.5° C. Form: Free EXAMPLE140 ##STR226## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 215.5°-216.5° C. Form: Free EXAMPLE141 ##STR227## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 211.5°-212.5° C. Form: Free EXAMPLE142 ##STR228## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 280.5°-281.5° C. Form: Free EXAMPLE143 ##STR229## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 235.5°-236.5° C. Form: Free EXAMPLE144 ##STR230## Crystalline form: White powder Recrystallization solvent:Ethanol/dichloromethane Melting Point: 249.5°-250.5° C. Form: FreeEXAMPLE 145 ##STR231## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 217°-218° C. Form: FreeEXAMPLE 146 ##STR232## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 201.5°-203° C. Form: FreeEXAMPLE 147 ##STR233## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 221°-222° C. Form: FreeEXAMPLE 148 ##STR234## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 193°-194° C. Form: FreeEXAMPLE 149 ##STR235## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 176°-177° C. Form: FreeEXAMPLE 150 ##STR236## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 188°-189.5° C. Form: FreeEXAMPLE 151 ##STR237## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 227°-228° C. Form: FreeEXAMPLE 152 ##STR238## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 186°-187° C. Form: FreeEXAMPLE 153 ##STR239## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 135°-136° C. Form: FreeEXAMPLE 154 ##STR240## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 173°-174° C. Form: FreeEXAMPLE 155 ##STR241## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 174.5°-175.5° C. Form:Free EXAMPLE 156 ##STR242## Crystalline form: White powderRecrystallization solvent: Ethanol/diethyl ether Melting Point:156°-157° C. Form: Free EXAMPLE 157 ##STR243## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:153°-154° C. Form: Free EXAMPLE 158 ##STR244## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:169°-170° C. Form: Free EXAMPLE 159 ##STR245## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:185°-186° C. Form: Free EXAMPLE 160 ##STR246## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:213°-214° C. Form: Free EXAMPLE 161 ##STR247## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:240°-241° C. Form: Free EXAMPLE 162 ##STR248## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:225°-226° C. Form: Free EXAMPLE 163 ##STR249## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:209.5°-210.5° C. Form: Free EXAMPLE 164 ##STR250## Crystalline form:White powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 198°-199° C. Form: Free EXAMPLE 165 ##STR251## Crystalline form:White powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 214.5°-215.5° C. Form: Free EXAMPLE 166 ##STR252## Crystallineform: White powder Recrystallization solvent: Ethanol/diethyl etherMelting Point: 196.5°-197.5° C. Form: Free EXAMPLE 167 ##STR253##Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 194°-195° C. Form: Free EXAMPLE 168##STR254## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 191°-192° C. Form: Free EXAMPLE 169##STR255## Crystalline form: White powder Recrystallization solvent:Dichloromethane/ethanol Melting Point: 227°-228° C. Form: Free EXAMPLE170 ##STR256## Crystalline form: White powder Recrystallization solvent:Dichloromethane/diethyl ether Melting Point: 182°-183° C. Form: FreeEXAMPLE 171 ##STR257## Crystalline form: White powder Recrystallizationsolvent: Dichloromethane/diethyl ether Melting Point: 222°-223° C. Form:Free EXAMPLE 172 ##STR258## Crystalline form: White powderRecrystallization solvent: Dichloromethane/diethyl ether Melting Point:204°-205° C. Form: Free EXAMPLE 173 ##STR259## Crystalline form: Whitepowder Recrystallization solvent: Dichloromethane/diethyl ether MeltingPoint: 194°-195° C. Form: Free EXAMPLE 17 ##STR260## Crystalline form:White powder Recrystallization solvent: Dichloromethane/diethyl etherMelting Point: 213°-214° C. Form: Free EXAMPLE 175 ##STR261##Crystalline form: White powder Recrystallization solvent:Dichloromethane/diethyl ether Melting Point: 201°-202° C. Form: FreeEXAMPLE 176 ##STR262## Crystalline form: Colorless needlesRecrystalization solvent: Dichloromethane/diethyl ether Melting Point:173°-174° C. Form: Free EXAMPLE 177 ##STR263## Crystalline form: Whitepowder Recrystallization solvent: Dichloromethane/diethyl ether MeltingPoint: 150.5°-151.5° C. Form: Free EXAMPLE 178 ##STR264## Crystallineform: White powder Recrystallization solvent: Dichloromethane/diethylether Melting Point: 207.5°-208.5° C. Form: Free EXAMPLE 179 ##STR265##Crystalline form: White powder Recrystallization solvent:Dichloromethane/diethyl ether Melting Point: 256.5°-257.5° C. Form: FreeEXAMPLE 180 ##STR266## Crystalline form: White powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 199.5°-200.5° C. Form:Free EXAMPLE 181 ##STR267## Crystalline form: White powderRecrystallization solvent: Ethanol/diethyl ether Melting Point:211°-212° C. Form: Free EXAMPLE 182 ##STR268## Crystalline form: Whitepowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:189.5°-190.5° C. Form: Free EXAMPLE 183 ##STR269## Crystalline form:White powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 176.5°-177.5° C. Form: Free EXAMPLE 184 ##STR270## Crystallineform: Yellow powder Recrystallization solvent: Ethanol/diethyl etherMelting Point: 202°-203° C. Form: Free EXAMPLE 185 ##STR271##Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 219°-220° C. Form: Free EXAMPLE 186##STR272## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 272°-273° C. Form: Free EXAMPLE 187##STR273## Crystalline form: Yellow powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 146°-147° C. Form: Free EXAMPLE 188##STR274## Crystalline form: Yellow powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 229.5°-230.5° C. Form: Free EXAMPLE189 ##STR275## Crystalline form: Yellow powder Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 119.5°-120.5° C. Form:Free EXAMPLE 190 ##STR276## Crystalline form: Yellow powderRecrystallization solvent: Ethanol/diethyl ether Melting Point:189°-190° C. Form: Free EXAMPLE 191 ##STR277## Crystalline form: Yellowpowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:207°-208° C. Form: Free EXAMPLE 192 ##STR278## Crystalline form: Yellowpowder Recrystallization solvent: Ethanol/diethyl ether Melting Point:196.5°-197.5° C. Form: Free EXAMPLE 193 ##STR279## Crystalline form:Yellow powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 182°-183° C. Form: Free EXAMPLE 194 ##STR280## Crystalline form:Yellow powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 172°-173° C. Form: Free EXAMPLE 195 ##STR281## Crystalline form:Yellow powder Recrystallization solvent: Ethanol/diethyl ether MeltingPoint: 197.5°-198.5° C. Form: Free EXAMPLE 196 ##STR282## Crystallineform: Yellow powder Recrystallization solvent: Ethanol/diethyl etherMelting Point: 227°-228° C. Form: Free EXAMPLE 197 ##STR283##Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 216.5°-217.5° C. Form: Free EXAMPLE198 ##STR284## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 207°-208° C. Form: Free EXAMPLE 199##STR285## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 236°-237° C. Form: Free EXAMPLE 200##STR286## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 199.5°-200.5° C. Form: Free EXAMPLE201 ##STR287## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 171.5°-172.5° C. Form: Free EXAMPLE202 ##STR288## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 222.5°-223.5° C. Form: Free EXAMPLE203 ##STR289## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 209.5°-210.5° C. Form: Free EXAMPLE204 ##STR290## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 14) Form: Hydrochloride EXAMPLE 205##STR291## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 15) Form: Hydrochloride EXAMPLE 206##STR292## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 16) Form: Hydrochloride EXAMPLE 207##STR293## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 17) Form: Hydrochloride EXAMPLE 208##STR294## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 18) Form: Hydrochloride EXAMPLE 209##STR295## Crystalline form: Yellow powder Recrystallization solvent:Ethanol/water NMR analysis: 19) Form: Hydrochloride EXAMPLE 210##STR296## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 20) Form: Hydrochloride EXAMPLE 211##STR297## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 159.5°-160.5° C. Form: Free EXAMPLE212 ##STR298## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 189.5°-190.5° C. Form: Free EXAMPLE213 ##STR299## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 170.5°-171.5° C. Form: Free EXAMPLE214 ##STR300## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 165°-166° C. Form: Free Example 215##STR301## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 173.5°-174.5° C. Form: Free EXAMPLE216 ##STR302## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 182°-183° C. Form: Free EXAMPLE 217##STR303## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 225.5°-226.5° C. Form: Free EXAMPLE219 ##STR304## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 21) Form: Hydrochloride EXAMPLE 220##STR305## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 147.5°-148.5° C. Form: Free EXAMPLE221 ##STR306## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 136°-137° C. Form: Free EXAMPLE 222##STR307## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 191.5°-192.5° C. Form: Free EXAMPLE223 ##STR308## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 145°-146° C. Form: Free EXAMPLE 224##STR309## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 22) Form: Hydrochloride EXAMPLE 225##STR310## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 23) Form: Hydrochloride EXAMPLE 226##STR311## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 24) Form: Hydrochloride EXAMPLE 227##STR312## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 25) Form: Hydrochloride EXAMPLE 228##STR313## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 26) Form: Hydrochloride EXAMPLE 229##STR314## Crystalline form: White powder Recrystallization solvent:Ethanol/water NMR analysis: 27) Form: Hydrochloride EXAMPLE 230##STR315## Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 206°-207° C. Form: Free EXAMPLE 231##STR316## Crystalline form: White powder Recrystallization solvent:Chloroform/methanol Melting Point: 211°-213° C. Form: Free EXAMPLE 232##STR317## Crystalline form: White powder Recrystallization solvent:Chloroform/methanol Melting, Point: 228.5°-229.5° C. Form: Free EXAMPLE233 ##STR318## Crystalline form: White powder Recrystallization solvent:Chloroform/methanol Melting Point: 237°-238° C. Form: Free EXAMPLE 234##STR319## Crystalline form: White powder Recrystallization solvent:Chloroform/methanol Melting Point: 226°-228° C. Form: Free EXAMPLE 235##STR320## Crystalline form: White powder Recrystallization solvent:Chloroform/methanol Melting Point: 220°-222° C. Form: Free EXAMPLE 236##STR321## Crystalline form: Colorless amorphous NMR analysis: 28) Form:Free EXAMPLE 237 ##STR322## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 162°-165° C. Form:Free EXAMPLE 238 ##STR323## Crystalline form: Light brown amorphous NMRanalysis: 29) Form: Free EXAMPLE 239 ##STR324## Crystalline form: Lightbrown amorphous NMR analysis: 30) Form: Free EXAMPLE 240 ##STR325##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 215°-217° C. Form: Free EXAMPLE 241 ##STR326##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 221°-223° C. Form: Free EXAMPLE 242 ##STR327##Crystalline form: Colorless amorphous NMR analysis: 31) Form: FreeEXAMPLE 243 ##STR328## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 207°-210° C. Form: Free EXAMPLE 244##STR329## Crystalline form: Colorless amorphous NMR analysis: 32) Form:Free EXAMPLE 245 ##STR330## Crystalline form: Colorless amorphous NMRanalysis: 33) Form: Free EXAMPLE 246 ##STR331## Crystalline form:Colorless amorphous NMR analysis: 34) Form: Free EXAMPLE 247 ##STR332##Crystalline form: Colorless amorphous NMR analysis: 35) Form: FreeEXAMPLE 248 ##STR333## Crystalline form: Light yellow powderRecrystallization solvent: Ethanol Melting Point: 186°-187° C. Form:Free EXAMPLE 249 ##STR334## Crystalline form: Color less needlesRecrystallization solvent: Ethanol Melting Point: 190°-191° C. Form:Free EXAMPLE 250 ##STR335## Crystalline form: Light yellow scalesRecrystallization solvent: Ethanol/water Melting Point: 230°-231° C.Form: Free EXAMPLE 251 ##STR336## Crystalline form: Light yellow needlesRecrystallization solvent: Ethanol Melting Point: 227°-228° C. Form:Free EXAMPLE 252 ##STR337## Crystalline form: Colorless needlesRecrystallization solvent: Ethyl acetate Melting Point: 192° C. Form:Free EXAMPLE 253 ##STR338## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 186.5°-189° C.Form: Free EXAMPLE 254 ##STR339## Crystalline form: Light yellow scalesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:165°-167° C. Form: Free EXAMPLE 255 ##STR340## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate Melting Point: 169°-170°C. Form: Free EXAMPLE 256 ##STR341## Crystalline form: Colorless scalesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:174°-177° C. Form: Free EXAMPLE 257 ##STR342## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate Melting Point: 114°-118°C. Form: Free EXAMPLE 258 ##STR343## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 170°-172° C.Form: Free EXAMPLE 259 ##STR344## Crystalline form: White powderRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:179°-181° C. Form: Free EXAMPLE 260 ##STR345## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate Melting Point: 118°-121°C. Form: Free EXAMPLE 261 ##STR346## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 144°-148° C.Form: Free EXAMPLE 262 ##STR347## Crystalline form: Colorless scalesRecrystallization solvent: Ethyl acetate Melting Point: 156°-157° C.Form: Free EXAMPLE 263 ##STR348## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 204°-206° C.Form: Free EXAMPLE 264 ##STR349## Crystalline form: Light yellow powderRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:165°-167° C. Form: Free EXAMPLE 265 ##STR350## Crystalline form: Lightyellow amorphous NMR analysis: 36) Form: Free EXAMPLE 266 ##STR351##Crystalline form: White powder Recrystallization solvent: n-Hexane/ethylacetate Melting Point: 122°-124° C. Form: Free EXAMPLE 267 ##STR352##Crystalline form: Light yellow powder Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 116°-117° C. Form: Free EXAMPLE268 ##STR353## Crystalline form: White powder Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 121°-123° C. Form: Free EXAMPLE269 ##STR354## Crystalline form: Colorless needles Recrystallizationsolvent: Ethyl acetate Melting Point: 186°-187° C. Form: Free EXAMPLE270 ##STR355## Crystalline form: White powder Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 139°-142° C. Form: Free EXAMPLE271 ##STR356## Crystalline form: Light yellow amorphous NMR analysis:37) Form: Free EXAMPLE 272 ##STR357## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 149.5°-152.5° C.Form: Free EXAMPLE 273 ##STR358## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol Melting Point: 150°-152.5° C. Form:Free EXAMPLE 274 ##STR359## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 150° C. Form:Free EXAMPLE 275 ##STR360## Crystalline form: Colorless needlesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:101°-104° C. Form: Free EXAMPLE 276 ##STR361## Crystalline form: Whitepowder Recrystallization solvent: n-Hexane/ethyl acetate Melting Point:120°-122° C. Form: Free EXAMPLE 277 ##STR362## Crystalline form: Lightyellow amorphous NMR analysis: 38) Form: Free EXAMPLE 278 ##STR363##Crystalline form: Colorless needles Recrystallization solvent: EthanolMelting Point: 183°-186° C. Form: Free EXAMPLE 279 ##STR364##Crystalline form: Light brown powder Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 139°-142° C. Form: Free EXAMPLE280 ##STR365## Crystalline form: Light yellow powder Recrystallizationsolvent: Ethanol Melting Point: 162°-165° C. Form: Free EXAMPLE 281##STR366## Crystalline form: Light yellow scales Recrystallizationsolvent: Ethyl acetate Melting Point: 224°-227° C. Form: Free EXAMPLE282 ##STR367## Crystalline form: Light yellow amorphous NMR analysis:39) Form: Free EXAMPLE 283 ##STR368## Crystalline form: Light yellowpowder Recrystallization solvent: Ethanol/water Melting Point: 162°-164°C. Form: Free EXAMPLE 284 ##STR369## Crystalline form: Light yellowpowder Recrystallization solvent: Ethanol Melting Point: 238°-241° C.(decomposed) Form: Hydrochloride EXAMPLE 285 ##STR370## Crystallineform: Light yellow amorphous NMR analysis: 40) Form: Free EXAMPLE 286##STR371## Crystalline form: Colorless amorphous NMR analysis: 41) Form:Free EXAMPLE 287 ##STR372## Crystalline form: Colorless needlesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:168°-169° C. Form: Free EXAMPLE 288 ##STR373## Crystalline form: Lightbrown powder Recrystallization solvent: Ethanol Melting Point: 189°-191°C. Form: Free EXAMPLE 289 ##STR374## Crystalline form: White powderRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:200°-202° C. Form: Free EXAMPLE 290 ##STR375## Crystalline form:Colorless scales Recrystallization solvent: n-Hexane/ethyl acetateMelting Point: 143°-146° C. Form: Free EXAMPLE 291 ##STR376##Crystalline form: White powder Recrystallization solvent: n-Hexane/ethylacetate Melting Point: 117°-117.5° C. Form: Free EXAMPLE 292 ##STR377##Crystalline form: Light brown powder Recrystallization solvent: Diethylether/ethyl acetate Melting Point: 225°-226° C. Form: Free EXAMPLE 293##STR378## Crystalline form: White powder Recrystallization solvent:n-Hexane/ethanol Melting Point: 175°-176.5° C. Form: Free EXAMPLE 294##STR379## Crystalline form: White powder Recrystallization solvent:Ethyl acetate Melting Point: 234°-236° C. Form: Free EXAMPLE 295##STR380## Crystalline form: Colorless scales Recrystallization solvent:Ethyl acetate Melting Point: 172°-174° C. Form: Free EXAMPLE 296##STR381## Crystalline form: White powder Recrystallization solvent:Ethyl acetate Melting Point: 154°-155° C. Form: Free EXAMPLE 297##STR382## Crystalline form: Light yellow needles Recrystallizationsolvent: n-Hexane/ethyl acetate Melting Point: 181.5°-183.5° C. Form:Free EXAMPLE 298 ##STR383## Crystalline form: White powderRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:173°-175° C. Form: Free EXAMPLE 299 ##STR384## Crystalline form: Whitepowder Recrystallization solvent: n-Hexane/ethyl acetate Melting Point:137°-138° C. Form: Free EXAMPLE 300 ##STR385## Crystalline form: Lightyellow amorphous NMR analysis: 42) Form: Free EXAMPLE 301 ##STR386##Crystalline form: Colorless needles Recrystallization solvent: Diethylether/ethyl acetate Melting Point: 129°-130° C. Form: Free EXAMPLE 302##STR387## Crystalline form: Colorless needles Recrystallizationsolvent: n-Hexane/ethyl acetate Melting Point: 181°-183° C. Form: FreeEXAMPLE 303 ##STR388## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate Melting Point: 248°-249° C. Form: Free EXAMPLE304 ##STR389## Crystalline form: Light yellow amorphous NMR analysis:43) Form: Free EXAMPLE 305 ##STR390## Crystalline form: Light yellowneedles Recrystallization solvent: Ethanol Melting Point: 94°-96° C.Form: Free EXAMPLE 306 ##STR391## Crystalline form: Light brown powderRecrystallization solvent: Ethyl acetate Melting Point: 159°-161° C.Form: Free EXAMPLE 307 ##STR392## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 180°-183° C.Form: Free EXAMPLE 308 ##STR393## Crystalline form: Light brown powderRecrystallization solvent: Ethanol Melting Point: 177°-180° C. Form:Free EXAMPLE 309 ##STR394## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 91°-93° C. Form:Free EXAMPLE 310 ##STR395## Crystalline form: Light brown scalesRecrystallization solvent: Ethanol Melting Point: 155°-156.5° C. Form:Free EXAMPLE 311 ##STR396## Crystalline form: Colorless scalesRecrystallization solvent: Ethyl acetate Melting Point: 172.5°-175° C.Form: Free EXAMPLE 312 ##STR397## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 148°-150.5° C. Form:Free EXAMPLE 313 ##STR398## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 172°-173° C.Form: Free EXAMPLE 314 ##STR399## Crystalline form: Colorless scalesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:133°-135° C. Form: Free EXAMPLE 315 ##STR400## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate Melting Point: 217°-219°C. Form: Free EXAMPLE 316 ##STR401## Crystalline form: Colorless needlesRecrystallization solvent: Ethyl acetate Melting Point: 226°-227.5° C.Form: Free EXAMPLE 317 ##STR402## Crystalline form: Colorless amorphousNMR analysis: 44) Form: Free EXAMPLE 318 ##STR403## Crystalline form:White powder Recrystallization solvent: Dichloromethane Melting Point:234°-235° C. Form: Free EXAMPLE 319 ##STR404## Crystalline form:Colorless prisms Recrystallization solvent: Methanol Melting Point:218°-218.5° C. Form: Free EXAMPLE 320 ##STR405## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol Melting Point:202.5°-206° C. Form: Free EXAMPLE 321 ##STR406## Crystalline form: Whitepowder Recrystallization solvent: Ethanol Melting Point: 174°-176° C.Form: Free EXAMPLE 322 ##STR407## Crystalline form: Colorless prismsRecrystallization solvent:. Ethanol Melting Point: 216°-218° C. Form:Free EXAMPLE 323 ##STR408## Crystalline form: White powder MeltingPoint: >300° C. NMR analysis: 45) Form: Free EXAMPLE 324 ##STR409##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 250.5°-251° C. Form: Free EXAMPLE 325 ##STR410##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 223°-225° C. Form: Free EXAMPLE 326 ##STR411##Crystalline form: Colorless prismsr Recrystallization solvent: MethanolMelting Point: 213°-214° C. Form: Free EXAMPLE 327 ##STR412##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 246°-247° C. Form: Free EXAMPLE 328 ##STR413##Crystalline form: Colorless prisms Recrystallization solvent: MethanolMelting Point: 248°-251° C. Form: Free EXAMPLE 329 ##STR414##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 268.5°-270.5° C. Form: Free EXAMPLE 330 ##STR415##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 174°-176° C. Form: HydrochlorideEXAMPLE 331 ##STR416## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 130°-134° C. Form: Free EXAMPLE 332##STR417## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 214°-217° C. Form: HydrochlorideEXAMPLE 333 ##STR418## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 218°-220° C. Form:Hydrochloride EXAMPLE 334 ##STR419## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 222°-225° C.Form: Free EXAMPLE 335 ##STR420## Crystalline form: Colorless needlesRecrystallization solvent: Methanol/diethyl ether Melting Point:171°-172° C. Form: Free EXAMPLE 336 ##STR421## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:235.5°-236° C. Form: Dihydrochloride EXAMPLE 337 ##STR422## Crystallineform: White powder Recrystallization solvent: Methanol/diethyl etherMelting Point: 241°-243° C. Form: Free EXAMPLE 338 ##STR423##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 187°-191° C. Form: Free EXAMPLE339 ##STR424## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 240°-244° C. Form: HydrochlorideEXAMPLE 340 ##STR425## Crystalline form: Colorless prismsRecrystallization solvent: Methanol/diethyl ether Melting Point:181°-182° C. Form: Free EXAMPLE 341 ##STR426## Crystalline form:Colorless prisms Recrystallization solvent: Methanol/diethyl etherMelting Point: 188°-190° C. Form: Dihydrochloride EXAMPLE 342 ##STR427##Crystalline form: White powder Recrystallization solvent: Isopropylalcohol Melting Point: 218°-218.5° C. Form: Hydrochloride EXAMPLE 343##STR428## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 243°-245.5° C. Form: Free EXAMPLE344 ##STR429## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 130°-133° C. Form: Free EXAMPLE345 ##STR430## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 155°-158° C. Form: Free EXAMPLE346 ##STR431## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 208°-210° C. Form: HydrochlorideEXAMPLE 347 ##STR432## Crystalline form: Colorless prismsRecrystallization solvent: Methanol/diethyl ether Melting Point:154°-155° C. Form: Hydrochloride EXAMPLE 348 ##STR433## Crystallineform: White powder Recrystallization solvent: Methanol/diethyl etherMelting Point: 142°-143° C. Form: Free EXAMPLE 349 ##STR434##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 120°-125° C. Form: HydrochlorideEXAMPLE 350 ##STR435## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 91°-95° C. Form:Hydrochloride EXAMPLE 351 ##STR436## Crystalline form: White powderRecrystallization solvent: Methanol/diethyl ether Melting Point:145°-146.5° C. Form: Free EXAMPLE 352 ##STR437## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:105°-105.5° C. Form: Free EXAMPLE 353 ##STR438## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:151°-155° C. Form: Dihydrochloride EXAMPLE 354 ##STR439## Crystallineform: White powder Recrystallization solvent: Methanol/diethyl etherMelting Point: 135.5°-137.5° C. Form: Free EXAMPLE 355 ##STR440##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 178°-178.5° C. Form: Free EXAMPLE 356 ##STR441##Crystalline form: White powder Recrystallization solvent:Dichloromethane Melting Point: 266.5°-268° C. Form: Free EXAMPLE 357##STR442## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 123°-124° C. Form: Free EXAMPLE358 ##STR443## Crystalline form: White powder Recrystallization solvent:Ethyl acetate Melting Point: 212°-213.5° C. Form: Free EXAMPLE 359##STR444## Crystalline form: Colorless scales Recrystallization solvent:Ethyl acetate Melting Point: 160.5°-162° C. Form: Free EXAMPLE 360##STR445## Crystalline form: Colorless needles Recrystallizationsolvent: Ethanol Melting Point: 103°-105° C. Form: Free EXAMPLE 361##STR446## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 145°-146° C. Form: Free EXAMPLE 362 ##STR447##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 247°-250° C. Form: Free EXAMPLE363 ##STR448## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 198°-199° C. Form: Free EXAMPLE364 ##STR449## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 181.5°-182.5° C. Form: FreeEXAMPLE 365 ##STR450## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 170°-170.5° C. Form: FreeEXAMPLE 366 ##STR451## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 156°-158° C. Form:Hydrochloride EXAMPLE 367 ##STR452## Crystalline form: White powderRecrystallization solvent: Diethyl ether Melting Point: 168.5°-170.5° C.Form: Free EXAMPLE 368 ##STR453## Crystalline form: White powderRecrystallization solvent: Methanol/diethyl ether Melting Point:177°-181.5° C. Form: Hydrochloride EXAMPLE 369 ##STR454## Crystallineform: White powder Recrystallization solvent: Methanol/diethyl etherMelting Point: 211°-213° C. Form: Free EXAMPLE 370 ##STR455##Crystalline form: White powder NMR analysis: 46) Form: Free EXAMPLE 371##STR456## Crystalline form: White powder Recrystallization solvent:Methanol/ethyl acetate Melting Point: 166°-167° C. Form: Free EXAMPLE372 ##STR457## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 127°-131° C. Form: Free EXAMPLE373 ##STR458## Crystalline form: White powder Recrystallization solvent:Methanol Melting Point: 170°-171° C. Form: Free EXAMPLE 374 ##STR459##Crystalline form: White powder Recrystallization solvent: MethanolMelting Point: 125°-126° C. Form: Free EXAMPLE 375 ##STR460##Crystalline form: Light yellow amorphous NMR analysis: 47) Form:Hydrochloride EXAMPLE 376 ##STR461## Crystalline form: Colorlessamorphous NMR analysis: 48) Form: Hydrochloride

¹ H-NMR (CDCl₃) δ: 1.92 (1H, t, J=6.2 Hz), 1.98 (1H, t, J=6.4 Hz), 2.8(2H, J=6.4 HZ), 3.76 (2H, t, J=6.2 Hz), 6.75 (1B, J=7.6 Hz), 6.86 (2H,d, J=8.6 Hz), 6.8-7.1 (2H, m), 7.20 (1H, d, J=7 Hz), 7.30 (2H, d, J=8.6Hz), 7.72 (2H, d, J=8.6 Hz), 7.84 (2H, d, J=8.6 Hz), 10.13 (1H, s)

2) ¹ H-NMR (DMSO-d₆) δ: 2.05 (2H, quint, J=6.4 Hz), 2.91 (2H, t, J=6.4Hz), 3.86 (2H, t, J=6.4 Hz), 6.85 (1H, d, J=7.6 Hz), 6.9-7.2 (2H, m),7.30 (1H, d, J=7.2 Hz), 7.44 (2H, d, J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz),8.1-8.2 (4H, m), 10.65 (1H, s), 13.2-13.4 (1H, br)

3) ¹ H-NMR (CDCl₃) δ: 1.9-2.1 (2H, m), 2.84 (2H, t, J=6.5 Hz), 3.82 (6H,s), 3.90 (2H, t, J=6.6 Hz), 6.5-7.2 (7H, m), 7.35 (2H, d, J=8.7 Hz),7.55 (2H, d, J=8.7 Hz), 8.05 (1H, s)

4) ¹ H-NMR (CDCl₃) δ: 1.9-2.1 (2H, m), 2.37 (6H, s), 2.84 (2H, t, J=6.6Hz), 3.90 (2H, t, J=6.6 Hz), 6.71 (1H, d, J=7.9 Hz), 6.8-7.2 (4H, m),7.35 (2H, d, J=8.6 Hz), 7.44 (2H, s), 7.56 (2H, d, J=8.6 Hz), 8.00 (1H,s)

5) ¹ H-NMR (CDCl₃) δ: 1.9-2.2 (2H, m), 2.12 (3H, s), 2.84 (2H, t, J=6.6Hz), 3.89 (2H, t, J=6.5 Hz), 6.71 (1H, d, J=7.8 Hz), 6.87 (1H, t, J=7Hz), 6.99 (1H, t, J=7.3 Hz), 7.15 (1H, d, J=6.5 Hz), 7.28 (2H, d, J=8.6Hz), 7.41 (2H, d, J=8.6 Hz), 8.03 (1H, s)

6) ¹ H-NMR (CDCl₃) δ: 0.8-1.3 (6H, m), 1.6-2.3 (9H, m), 2.83 (2H, t,J=6.6 Hz), 3.89 (2H, t, J=6.5 Hz), 6.72 (1H, d, J=7.9 Hz), 6.8-7.1 (2H,m), 7.15 (1H, d, J=7.4 Hz), 7.28 (2H, d, J=8.3 Hz), 7.44 (2H, d, J=8.4Hz), 7.9-8.1 (1H, m)

7) ¹ H-NMR (CDCl₃) δ: 2.02 (2H, quint, J=6.5 Hz), 2.81 (2H, t, J=6.6Hz), 3.69 (2H, s), 3.87 (2H, t, J=6.6 Hz), 6.66 (1H, d, J=8.2 Hz),6.8-7.0 (2H, m), 7.13 (1H, d, J=7.3 Hz), 7.2-7.4 (9H, m), 7.59 (1H, s)

8) ¹ H-NMR (CDCl₃) δ: 1.7-2.1 (17H, m), 2.83 (2H, t, J=6.7 Hz), 3.90(2H, t, J=6.6 Hz), 6.68 (1H, d, J=8.1 Hz), 6.8-7.1 (2H, m), 7.14 (1H, d,J=7 Hz), 7.32 (2H, d, J=8.7 HZ), 7.39 (1H, s), 7.46 (2H, d, J=8.7 Hz)

9) ¹ H-NMR (CDCl₃) δ: 1.99 (2H, quint, J=6.5 Hz), 2.82 (2H, t, J=6.6Hz), 3.82 (2H, t, J=6.5 Hz), 6.8-7.1 (4H, m), 7.1-7.3 (2H, m), 7.4-7.6(3H, m), 7.67 (1H, s), 7.8-8.0 (3H, m), 8.42 (1H, s)

10) ¹ H-NMR (CDCl₃) δ: 2.00 (2H, quint, J=6.5 Hz), 2.83 (2H, t, J=6.6Hz), 3.85 (2H, t, J=6.6 Hz), 3.86 (3H, s), 6.8-7.1 (6H, m), 7.1-7.3 (2H,m), 7.64 (1H, s), 7.8-8.0 (3H, m), 8.22 (1H, s)

11) ¹ H-NMR (CDCl₃) δ: 1.98 (2H, quint, J=6.5 Hz), 2.82 (2H, t, J=6.5Hz), 3.81 (2H, t, J=6.5 Hz), 3.84 (3H, s), 6.8-7.5 (10H, m), 7.68 (1H,s), 7.95 (1H, d, J=8.2 Hz), 8.52 (1H, s)

12) ¹ H-NMR (CDCl₃) δ: 1.7-1.9 (2H, m), 2.70 (2H, t, J=6.6 Hz), 3.70(2H, t, J=6.4 Hz), 6.8-7.3 (6H, m), 7.4-7.7 (2H, m), 7.8-7.9 (5H, m),8.04 (1H, d, J=8 Hz), 8.33 (1H, s), 8.90 (1H, s)

13) ¹ H-NMR (CDCl₃) δ: 1.7-2.1 (17H, m), 2.84 (2H, t, J=6.5 Hz), 3.89(2H, t, J=6.4 Hz), 6.8-7.2 (6H, m), 7.42 (1H, s), 7.56 (1H, s), 7.81(1H, d, J=8.1 Hz)

14) ¹ H-NMR (DMSO-d₆) δ: 1.0-1.5 (5H, m), 1.5-2.0 (5H, m), 2.2-3.8 (5H,m), 4.2-5.2 (3H, m), 6.77 (1H, d, J=7.2 Hz), 7.1-7.4 (4H, m), 7.47 (2H,d, J=8.6 Hz), 7.58 (1H, d, J=6.2 Hz), 10.06 (1H, s), 10.9-12.1 (1H, br)

15) ¹ H-NMR (DMSO-d₆) δ: 2.5-3.8 (6H, m), 4.2-5.2 (3H, m), 6.81 (5H, d,J=6.8 Hz), 7.1-7.3 (4H, m), 7.5-7.7 (3H, m), 7.8-8.0 (1H, m), 7.97 (2H,d, J=1.8 Hz), 10.66 (1H, s), 11.1-12.3 (1H, br)

16) ¹ H-NMR (DMSO-d₆) δ: 2.20 (3H, s), 2.27 (3H, s), 2.5-3.8 (6H, m),4.3-5.3 (3H, m), 6.82 (1H, d, J=7.2 Hz), 7.1-7.4 (7H, m), 7.5-7.8 (3H,m), 10.43 (1H, s), 11.0-12.2 (1H, br)

17) ¹ H-NMR (DMSO-d₆) δ: 2.34 (3H, s), 2.5-3.7 (6H, m), 4.3-5.2 (3H, m),6.82 (1H, d, J=6.8 Hz), 7.2-7.7 (11H, m), 10.41 (1H, s), 10.8-12.3 (1H,br)

18) ¹ H-NMR (DMSO-d₆) δ: 2.38 (3H, s), 2.5-3.8 (6H, m), 4.3-5.3 (3H, m),6.81 (1H, d, J=7.0 Hz), 7.1-7.5 (6H, m), 7.5-7.8 (5H, m), 10.35 (1H, s),10.9-12.2 (1H, br)

19) ¹ H-NMR (DMSO-d₆) δ: 2.37 (3H, s), 2.5-3.7 (6H, m), 4.3-5.2 (3H, m),6.81 (1H, d, J=7.2 Hz), 7.2-7.4 (6H, m), 7.5-7.7 (3H, m), 7.84 (2H, d,J=8.0 Hz), 10.31 (1H, s), 10.9-12.2 (1H, br)

20) ¹ H-NMR (DMSO-d₆) δ: 2.5-3.8 (6H, m), 4.3-5.2 (3H, m), 6.82 (1H, d,J=7.4 Hz), 7.2-7.3 (4H, m), 7.5-7.8 (5H, m), 7.75 (1H, d, J=1.8 Hz),10.70 (1H, s), 10.8-12.2 (1H, br)

21) ¹ H-NMR (DMSO-d₆) δ: 2.5-3.8 (9H, m), 4.3-4.7 (1H, m), 4.7-5.1 (2H,m), 6.8-7.1 (3H, m), 7.1-7.4 (2H, m), 7.5-7.7 (2H, m), 7.8-8.0 (3H, m),9.79 (1H, s), 10.8-12.2 (1H, br)

22) ¹ H-NMR (DMSO-d₆) δ: 0.8-1.2 (3H, m), 1.7-2.2 (2H, m), 2.5-3.8 (5H,m), 4.3-5.2 (3H, m ), 6.80 (1H, d, J=7.2 Hz), 7.1-7.3 (4H, m), 7.6-7.7(3H, m), 7.85 (1H, s), 7.96 (2H, d, J=1.8 Hz), 10.62 (1H, s), 10.8-12.0(1H, br)

23) ¹ H-NMR (DMSO-d₆) δ: 0.8-1.1 (3H, m), 1.7-2.1 (2H, m), 2.37 (3H, s),2.7-3.8 (5H, m), 4.4-5.2 (3H, m), 6.81 (1H, d, J=7.6 Hz), 7.2-7.4 (6H,m), 7.6-7.7 (3H, m), 7.84 (2H, d, J=8.2 Hz), 10.29 (1H, s), 10.5-11.8(1H, br)

24) ¹ H-NMR (DMSO-d₆) δ: 0.8-1.2 (3H, m), 1.7-2.1 (2H, m), 2.38 (3H, s),2.6-3.8 (5H, m), 4.3-5.2 (3H, m), 6.81 (1H, d, J=7.0 Hz), 7.2-7.5 (6H,m), 7.6-7.8 (5H, m), 10.33 (1H, s), 10.5-11.7 (1H, br)

25) ¹ H-NMR (DMSO-d₆) δ: 0.8-1.2 (3H, m), 1.7-2.1 (2H, m), 2.6-3.8 (5H,m), 3.8-5.2 (3H, m), 6.82 (1H, d, J=7.2 Hz), 7.1-7.5 (5H, m), 7.5-7.7(3H, m), 10.42 (1H, s), 10.7-12.0 (1H, br)

26) ¹ H-NMR (DMSO-d₆) δ: 0.8-2.0 (15H, m), 2.2-2.5 (1H, m), 2.6-3.7 (5H,m), 4.3-5.2 (3H, m), 6.76 (1H, d, J=7.0 Hz), 7.1-7.4 (4H, m), 7.46 (2H,d, J=8.6 Hz), 7.61 (1H, d, J=6.4 Hz), 10.03 (1H, s), 10.5-11.8 (1H, br)

27) ¹ H-NMR (DMSO-d₆) δ: 0.8-1.1 (3H, m), 1.7-2.0 (2H, m), 2.20 (3H, s),2.29 (3H, s), 2.6-3.7 (5H, m), 4.3-5.2 (3H, m), 6.82 (1H, d, J=7.0 Hz),7.2-7.4 (7H, m), 7.5-7.7 (3H, m), 10.41 (1H, s), 10.6-12.0 (1H, br)

28) ¹ H-NMR (CDCl₃) δ: 1.21 (3H, t, J=7.1 Hz), 3.00-3.25 (3H, m),4.00-4.30 (4H, m), 6.63 (1H, d, J=7.8 Hz), 6.86 (1H, t, J=7.3 Hz), 7.00(1H, t, J=6.3 Hz), 7.10-7.31 (3H, m), 7.40-7.57 (3H, m), 7.77 (2H, d,J=1.9 Hz), 8.76 (1H, brs)

29) ¹ H-NMR (CDCl₃) δ: 2.29 (3H, s), 2.32 (3H, s), 2.34 (3H, s),2.50-3.15 (11H, m), 3.79 (1H, dd, J=13.2 Hz, 7.3 Hz), 4.05 (1H, dd,J=13.2 Hz, 5.7 Hz), 6.62 (1H, d, J=7.7 Hz), 6.82-7.48 (8H, m), 7.53 (2H,d, J=8.4 Hz), 8.05 (1H, brs)

30) ¹ H-NMR (CDCl₃) δ: 1.65-2.01 (4H, m), 2.31 (3H, s), 2.35 (3H, s ),2.55-3.02 (6H, m), 3.09 (1H, dd, J=15 Hz, 5 Hz), 3.70 (1H, dd, J=12.5Hz, 8.0 Hz), 4.22 (1H, dd, J=12.5 Hz, 5 Hz), 6.67 (1H, d, J=7.8 Hz),6.80-7.32 (7H, m), 7.37 (2H, d, J=8.6 Hz), 7.53 (1H, d, J=8.3 Hz), 7.66(1H, brs)

31) ¹ H-NMR (CDCl₃) δ: 2.80 (1H, dd, J=16.1 Hz, 5.3 Hz), 3.16 (1H, dd,J=15.8 Hz, 5.3 Hz), 3.75-4.50 (3H, m), 4.87-5.10 (3H, m), 6.80-7.60(14H, m), 7.74 (2H, d, J=1.9 Hz), 8.47 (1H, brs)

32) ¹ H-NMR (CDCl₃) δ: 2.35 (6H, s), 2.72-3.10 (3H, m), 3.65-3.78 (1H,m), 4.06-4.18 (1H, m), 6.60-7.62 (9H, m), 7.74 (2H, d, J=1.8 Hz), 8.52(1H, brs)

33) ¹ H-NMR (CDCl₃) δ: 1.87 (3H, s), 2.68 (1H, dd, J=5.6 Hz, 16 Hz),3.14 (1H, dd, J=5.6 Hz, 16 Hz), 3.70-3.95 (2H, m), 4.32-4.50 (1H, m),6.29 (1H, d, J=7.6 Hz), 6.90-7.80 (11H, m), 9.16 (1H, brs)

34) ¹ H-NMR (CDCl₃) δ: 1.62 (1H, brs), 1.90-2.25 (2H, m), 2.55 (3H, s),3.78 (1H, t, J=5.1 Hz), 3.95 (2H, t, J=6.7 Hz), 6.69 (1H, t, J=7.9 Hz),6.90-7.13 (2H, m), 7.23-7.40 (3H, m), 7.42-7.56 (3H, m), 7.77 (2H, d,J=1.9 Hz), 8.53 (1H, brs)

35) ¹ H-NMR (CDCl₃) δ: 1.80-2.02 (1H, m), 2.20-2.35 (1H, m), 2.31 (6H,s), 3.52 (1H, t, J=5.4 Hz), 3.68-3.83 (1H, m), 3.95-4.15 (1H, m), 6.59(1H, d, J=7.8 Hz), 6.81-7.10 (2H, m), 7.16-7.50 (6H, m), 7.80 (2H, d,J=1.8 Hz), 9.13 (1H, brs)

36) ¹ H-NMR (CDCl₃) δ: 1.35-1.60 (1H, m), 1.65-2.20 (3H, m), 2.65-3.20(5H, m), 3.81 (2H, d, J=6.5 Hz), 4.90-5.10 (1H, m), 6.60 (1H, d, J=8.0Hz), 6.90 (1H, t, J=8.0 Hz), 7.00-7.50 (6H, m)

37) ¹ H-NMR (CDCl₃) δ: 1.30-2.25 (4H, m), 2.55-3.20 (3H, m), 3.35 (2H,s), 3.80 (2H, s), 4.90-5.10 (1H, m), 6.62 (1H, d, J=8.0 Hz), 6.85-7.45(12H, m), 9.27 (1H, brs)

38) ¹ H-NMR (CDCl₃) δ: 1.35-2.25 (4H, m), 2.33 (3H, s), 2.60-3.20 (3H,m), 3.12 (2H, s), 3.61 (2H, s), 5.00 (1H, brs), 6.50-7.60 (13H, m), 9.14(1H, brs)

39) ¹ H-NMR (CDCl₃) δ: 1.27 (3H, t, J=7.1 Hz), 1.25-2.50 (12H, m),2.70-3.10 (4H, m), 3.05 (2H, s), 4.15 (2H, q, J=7.0 Hz), 4.90-5.10 (1H,m), 6.63 (1H, d, J=7.5 Hz), 6.91 (1H, t, J=7.5 Hz), 7.00-7.50 (6H, m),9.14 (1H, brs)

40) ¹ H-NMR (CDCl₃) δ: 1.30-1.65 (1H, m), 1.80-2.25 (5H, m), 2.70-3.20(3H, m), 4.01 (2H, d, J=5.0 Hz), 4.90-5.10 (1H, m), 6.61 (1H, d, J=7.7Hz), 6.89 (1H, t, J=7.0 Hz), 7.00-7.45 (6H, m), 9.05 (1H, brs)

41) ¹ H-NMR (CDCl₃) δ: 1.18 (6H, s), 1.30-2.20 (4H, m), 2.60-3.20 (3H,m), 3.30 (2H, s), 3.73 (2H, s), 4.90-5.10 (1H, m), 6.61 (1H, d, J=7.3Hz), 6.70-7.45 (12H, m), 9.50 (1H, brs)

42) ¹ H-NMR (CDCl₃) δ: 1.19 (3H, t, J=7.0 Hz), 1.30-1.70 (1H, m),1.75-2.20 (3H, m), 2.65-3.15 (3H, m), 3.46 (2H, q, J=7.0 Hz), 3.88 (2H,s), 4.90-5.10 (1H, m), 6.55-7.45 (13H, m), 8.36 (1H, brs)

43) ¹ H-NMR (CDCl₃) δ: 1.08 (3H, t, J=7.2 Hz), 1.05-2.25 (14H, m),2.25-3.25 (10H, m), 4.90-5.10 (1H, m), 6.64 (1H, d, J=7.6 Hz), 6.90 (1H,t, J=7.2 Hz), 6.94-7.50 (6H, m), 11.50 (1H, brs)

44) ¹ H-NMR (CDCl₃) δ: 1.06 (3H, t, J=7.5 Hz ), 1.30-2.20 (6H, m),2.60-3.20 (3H, m), 3.65 (1H, m), 3.95 (1H, brs), 4.90-5.10 (1H, m),6.50-6.75 (3H, m), 6.75-7.05 (2H, m), 7.05-7.55 (5H, m), 8.67 (1H, brs)

45) ¹ H-NMR (DMSO-d₆) δ: 1.28-1.57 (1H, m), 1.69-2.20 (3H, m), 2.59-3.15(3H, m), 4.74-4.98 (1H, m), 6.62-6.80 (1H, m), 6.86-7.37 (5H, m),7.50-7.70 (2H, m), 8.95-9.02 (1H, m), 9.03-9.15 (2H, m), 10.85 (1H, s)

46) ¹ H-NMR (CDCl₃) δ: 1.40-1.66 (5H, m), 1.72-2.20 (7H, m), 2.63-3.18(3H, m), 3.42 (2H, t, J=6.7 Hz), 4.00 (2H, t, J=6.3 Hz), 4.91-5.13 (1H,m), 6.58-6.72 (1H, m), 6.82-7.00 (3H, m), 7.02-7.30 (4H, m), 7.36-7.51(2H, m), 7.70-7.88 (2H, m), 7.91 (1H, s)

47) ¹ H-NMR (DMSO-d₆) δ: 2.05-2.95 (8H, m), 3.43-3.70 (1H, m), 4.08-4.30(1H, m), 4.72-5.00 (1H, m), 6.70-8.08 (11H, m), 10.8 (1H, s), 11.1 (1H,brs)

48) ¹ H-NMR (DMSO-d₆) δ: 2.10-3.00 (8H, m), 3.47-3.70 (1H, m), 4.07-4.33(1H, m), 4.75-4.98 (1H, m), 6.78-6.91 (1H, m), 7.05-7.22 (2H, m),7.30-7.97 (9H, m), 10.75 (1H, s), 10.94 (1H, brs)

EXAMPLE 377

To a solution of1-[4-(4-formylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.3 g)in methanol (10 ml) is added gradually sodium borohydride (59 mg) underice-cooling and the mixture is stirred at room temperature for 2 hours.Water is added to the mixture and the solvent is distilled off underreduced pressure. The resulting residue is extracted withdichloromenhane, washed with water, and dried over magnesium sulfate.The solvent is distilled off under reduced pressure and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane methanol=50: 1), and recrystallized from methanol togive1-[4-(4-hydroxymethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(165 mg) as white powder, m.p. 224.5°-225.5° C.

Using the suitable starting materials, the compound of the above Example37 is obtained in the same manner as in Example 377.

EXAMPLE 378

To a solution of1-[4-(4-methoxycarbonylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5 g) in methanol (20 ml) is added 5% aqueous sodium hydroxidesolution (10 ml) and the mixture is stirred at room temperatureovernight. Methanol is distilled off under reduced pressure and theresulting residue is acidified with diluted aqueous hydrochloric acidsolution. The precipitated crystal is collected by filtration to give1-[4-(4-carboxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.4 g)as white powder, m.p. >300° C.

¹ H-NMR (DMSO-d₆) δ: 2.05 (2H, quint, J=6.4 Hz), 2.91 (2H, t, J=6.4 Hz),3.86 (2H, t, J=6.4 Hz), 6.85 (1H, d, J=7.6 Hz), 6.9-7.2 (2H, m), 7.30(1H, d, J=7.2 Hz), 7.44 (2H, d, J=8.5 Hz), 7.85 (2H, d, J=8.5 Hz),8.1-8.2 (4H, m), 10.65 (1H, s), 13.2-13.4 (1H, br)

Using the suitable starting materials, the compounds of the aboveExamples 39, 241, 252, 253 and 362 are obtained in the same manner as inExample 378.

EXAMPLE 379

To a solution of1-[4-(3-acetyloxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (1.5g) in methanol (20 ml) is added 5% aqueous sodium hydroxide solution (10ml) and the mixture is stirred at room temperature overnight. Methanolis distilled off under reduced pressure and the resulting residue isacidified with diluted aqueous hydrochloric acid solution. Theprecipitated crystal is collected by filtration and recrystallized frommethanol to give1-[4-(3-hydroxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (1.22g) as white powder, m.p. 217°-218° C.

Using the suitable starting materials, the compounds of the aboveExamples 10, 343, 356, 364 and 365 are obtained in the same manner as inExample 379.

EXAMPLE 380

To a solution of1-[4-(3-hydroxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.4 g)in acetone (5 ml) are added potassium carbonate (0.22 g) and ethyliodide (0.34 g), and the mixture is refluxed for 5 hours. Then, acetoneis distilled off under reduced pressure and water is added to theresidue. The precipitated crystal is collected by filtration, andrecrystallized from methanol to give1-[4-(3-ethoxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.36 g)as white powder, m.p. 170.5°-171.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 11, 12, 13, 14, 33, 35, 48, 50-55, 90-92, 97-100, 109-111,120-122, 136-138, 165-167, 175-177, 192-194, 211, 212, 214, 321, 322,330-333, 335, 336, 339-342, 344-355, 357-366 and 370-374 are obtained inthe same manner as in Example 380.

EXAMPLE 381

Ethanol (50 ml) is added to 10% Pd-C (0.1 g) and thereto isadded-1-[4-(3-nitrobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.73 g). The mixture is subjected to catalytic reduction at ordinarytemperature under atmospheric pressure of hydrogen. After completion ofthe reduction, 10% Pd-C is removed by filtration and the liltrate isconcentrated under reduced pressure. The residue is extracted withdichloromethane and the extract is dried over magnesium sulfate. Thesolvent is distilled off under reduced pressure and recrystallized frommethanol to give1-[4-(3-aminobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (0.54 g)as white powder, m.p. 205.5°-206.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 24, 334 and 338 are obtained in the same manner as in Example381.

EXAMPLE 382

To a solution of 1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline (0.5 g)in dichloromethane (20 ml) is added triethylamine (0.3 g), and theretois added benzoyl chloride (0.28 g) under ice-cooling. The mixture isstirred at room temperature for 1 hour. To the reaction mixture is addedwater and extracted with dichloromethane. The extract is dried overmagnesium sulfate and the solvent is distilled off under reducedpressure. The resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=50:1) andrecrystallized from methanol to give1-[4-(benzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline (245 mg) aswhite powder, m.p. 202.5°-203.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 2-119, 131-373, 375 and 376 are obtained in the same manner asin Example 382.

EXAMPLE 383

Thionyl chloride (10 ml) is added to1-(4-carboxybenzoyl)-1,2,3,4-tetrahydroquinoline (0.5 g) and the mixtureis refluxed for 1 hour. Thionyl chloride is distilled off under reducedpressure to give 4-[1-(1,2,3,4-tetrahydroquinolyl)carbonyl]benzoylchloride. Separately, to a solution of m-anisidine (0.27 g) indichloromethane (20 ml) is added triethylamine (0.34 g), and thereto isadded gradually the above obtained4-[1-(1,2,3,4-tetrahydroquinolyl)carbonyl]benzoyl chloride underice-cooling and the mixture is stirred at room temperature for 1 hour.Water is added to the reaction mixture and the mixture is extracted withdichloromethane. The extract is dried over magnesium sulfate. Thesolvent is distilled off under reduced pressure and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane: methanol=50:1), and recrystallized from methanol togive 1-[4-(3-methoxyanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline(203 mg) as colorless needles, m.p. 154°-155° C.

Using the suitable starting materials, the compounds of the aboveExamples 120, 122-130 and 374 are obtained in the same manner as inExample 383.

EXAMPLE 384

To4-oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.7g) are added tetrahyrdofuran (10 ml) and methanol (10 ml). To themixture is added sodium borohydride (0.1 g) in portions and the mixtureis stirred at room temperature for 1 hour. Water is added to thereaction mixture and the mixture is extracted with dichloromethane. Thesolvent is concentrated and the resulting residue is purified by silicagel column chromatography (eluent;dichloromethane→dichloromethane:methanol=20:1), and recrystallized fromethanol to give4-hydroxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.4 g) as white powder, m.p. 215°-217° C.

EXAMPLE 385

To3-ethoxycarbonyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.6 g) are added an aqueous solution of sodium hydroxide (0.1 g) inwater (1 ml) and ethanol (5 ml). The mixture is stirred at roomtemperature for 15 minutes, and acidified with diluted hydrochloricacid, extracted with dichloromethane. The solvent is distilled off andthe resulting residue is purified by silica gel column chromatography(eluent; dichloromethane→dichloromethane:methanol=50:1), andrecrystallized from ethanol to give3-carboxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.4 g) as white powder, m.p. 221°-223° C.

EXAMPLE 386

To3-carboxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(3.7 g) are added tetrahydrofuran (50 ml) and thionyl chloride (5 ml).The mixture is reacted at 60° C. for 1 hour. The reaction mixture isconcentrated and to the residue is added acetone (20 ml). To the mixtureis added dropwise a solution of sodium azide (1.0 g) in water (5 ml)under ice-cooling. The reaction mixture is stirred at the sametemperature for 30 minutes and extracted with dichloromethane, driedover magnesium sulfate. The solvent is concentrated and to the resultingresidue are added anhydrous toluene (30 ml) and benzyl alcohol (1.7 g).The mixture is refluxed for 1 hour. The reaction mixture is concentratedand the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane→dichloromethane:methanol=50:1)to give3-benzyloxycarbonylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl)-1,2,3,4-tetrahydroquinoline(3.7 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 2.80 (1H, dd, J=16.1 Hz, 5.3 Hz), 3.16 (1H, dd,J=15.8 Hz, 5.3 Hz), 3.75-4.50 (3H, m), 4.87-5.10 (3H, m), 6.80-7.60(14H, m), 7.74 (2H, d, J=1.9 Hz), 8.47 (1H, brs)

EXAMPLE 387

To3-benzyloxycarbonylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(3.3 g) are added acetic acid (40 ml) and 10% Pd-C (0.4 g) and thereaction mixture is subjected to catalytic reduction at ordinarytemperature under atmospheric pressure of hydrogen. One hour thereafter,the catalyst is removed by filtration and the filtrate is concentrated.The resulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=20:1), and recrystallized from ethanolto give3-amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(1.6 g) as white powder, m.p. 207°-210° C.

EXAMPLE 388

To3-amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5 g) are added methanol (10 ml), 37% formaline (0.8 ml) and sodiumcyanoborohydride (0.16 g). To the mixture is added acetic acid (0.5 ml)under ice-cooling and the mixture is stirred at room temperature for 1hour. Water is added to the reaction mixture and the mixture is basifiedwith potassium carbonate and extracted with dichloromethane. The solventis concentrated and the resulting residue is purified by silica gelcolumn chromatography (eluent; dichloromethane→dichloromethane:methanol=20:1) to give3-dimethylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.3 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 2.35 (6H, s), 2.72-3.10 (3H, m), 3.65-3.78 (1H, m),4.06-4.18 (1H, m), 6.60-7.62 (9H, m), 7.74 (2H, d, J=1.8 Hz), 8.52 (1H,brs)

Using the suitable starting materials, the compounds of the aboveExamples 246, 247, 375 and 376 are obtained in the same manner as inExample 388.

EXAMPLE 389

To3-amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.44 g) are added dichloromethane (5 ml) and acetic anhydride (0.12 g)and the mixture is stirred for 1 hour. The reaction mixture isconcentrated and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane→dichloromethane:methanol=50:1)to give3-acetylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.3 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 1.87 (3H, s), 2.68 (1H, dd, J=5.6 Hz, 16 Hz), 3.14(1H, dd, J=5.6 Hz, 16 Hz), 3.70-3.95 (2H, m), 4.32-4.50 (1H, m), 6.29(1H, d, J=7.6 Hz), 6.90-7.80 (11H, m), 9.16 (1H, brs)

Using the suitable starting materials, the compound of the above Example242 is obtained in the same manner as in Example 389.

EXAMPLE 390

To4-oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5g) are added 40% solution of methylamine in methanol (5 ml), molecularsieves 4A (1 g) and dimethylformamide (6 ml), and the mixture isrefluxed for 4 hours. After cooling, the reaction mixture is filteredand to the filtrate is added sodium borohydride (80 mg), and the mixtureis stirred at room temperature for 1 hour. The reaction mixture isconcentrated and water is added to the resulting residue, and extractedwith ethyl acetate. The solvent is concentrated and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane:methanol=20:1) to give4-methylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.2 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ: 1.62 (1H, brs), 1.90-2.25 (2H, m), 2.55 (3H, s), 3.78(1H, t, J=5.1 Hz), 3.95 (2H, t, J=6.7 Hz), 6.99 (1H, d, J=7.9 Hz),6.90-7.13 (2H, m)

Using the suitable starting materials, the compounds of the aboveExamples 238, 239, 244, 247, 375 and 376 are obtained in the same manneras in Example 390.

EXAMPLE 391

To3-carboxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.7 g) are added dimethylformamide (7 ml), diethyl cyanophosphate (0.3ml) and dimethylamine hydrochloride (0.15 g). Further thereto is addedtriethylamine (0.8 ml) and the mixture is stirred at room temperaturefor 1 hour. Water is added to the reaction mixture and extracted withethyl acetate. The solvent is concentrated and to the resulting residueis added diethyl ether. The precipitated crystal is collected byfiltration to give3-dimethylamido-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.5 g) as light yellow powder, m.p. 186°-187° C.

EXAMPLE 392

To a solution of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(3.0 g) in dichloromethane (50 ml) is added succinic anhydride (1.4 g)and the mixture is stirred at room temperature for 4.5 hours. Thereaction mixture is evaporated under reduced pressure in order to removethe solvent therefrom, and the resulting crystal is recrystallized fromethyl acetate to give1-[4-(3-carboxypropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3.61 g) as colorless needles, m.p. 192° C.

Using the suitable starting materials, the compound of the above Example253 is obtained in the same manner as in Example 392.

EXAMPLE 393

1-[4-(3-Carboxypropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.5 g) is dissolved in dimethylformamide (1 ml) and thereto is addeddropwise diethyl cyanophosphate (0.25 g) under ice-cooling. The mixtureis stirred at room temperature for 30 minutes and then cooled again withice. Thereto are added dropwise a solution of diethylamine (0.11 g) indimethylformamide (1 ml) and triethylamine (0.34 g). The mixture isstirred at room temperature for 16 hours. The solvent is distilled offunder reduced pressure and water is added to the resulting residue. Themixture is extracted with dichloromethane. The organic layer is washedsuccessively with diluted hydrochloric acid, water, saturated sodiumhydrogen carbonate solution, water and saturated saline solution, anddried over magnesium sulfate. The solvent is distilled off under reducedpressure and the resulting residue is purified by silica gel columnchromatography (eluent; ethyl acetate), and recrystallized fromn-hexane/ethyl acetate to give1-[4-(3-diethylaminocarbonylpropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.42 g) as colorless scales, m.p. 165°-167° C.

Using the suitable starting materials, the compounds of the aboveExamples 255-263 are obtained in the same manner as in Example 393.

EXAMPLE 394

To a solution of1-[4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.06 g) in dimethylformamide (5 ml) are added sodium iodide (0.90 g),potassium carbonate (1.1 g) and cyclohexylamine (0.89 g), and themixture is stirred at room temperature for 2 hours. Dimethylformamide isdistilled off under reduced pressure and water is added to the resultingresidue. The mixture is extracted with dichloromethane. The organiclayer is washed successively with water and saturated saline solution,and dried over magnesium sulfate. The solvent is distilled off underreduced pressure and the resulting residue is purified by silica gelcolumn chromatography (eluent; ethyl acetate), and recrystallized fromn-hexane/ethyl acetate to give1-[4-(2-cyclohexylaminoacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.03 g) as white powder, m.p. 139°-142° C.

Using the suitable starting materials, the compounds of the aboveExamples 271-309 and 317 are obtained in the same manner as in Example394.

EXAMPLE 395

o-Cresol (0.36 g) is dissolved in dimethylsulfoxide (4 ml) containingsodium hydroxide powder (0.18 g) and thereto is added1-[4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.03 g). The mixture is stirred at 90° C. for 7.5 hours. The reactionmixture is poured into ice-water (300 ml) and the precipitated crystalis collected by filtration, washed with water, and purified by silicagel column chromatography (eluent; n-hexane:ethyl acetate=2:1), andrecrystallized from ethyl acetate to give1-{4-[2-(2-methylphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(546 mg) as colorless scales, m.p. 172.5°-175° C.

Using the suitable starting materials, the compounds of the aboveExamples 310 and 312-316 are obtained in the same manner as in Example395.

EXAMPLE 396

A mixture of1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(2.00 g), sodium acetate (0.36 g), sodium iodide (0.55 g) and aceticacid (20 ml) is refluxed for 1 day. The solvent is distilled off and theresulting residue is extracted with ethyl acetate. The organic layer iswashed successively with 2N aqueous sodium hydroxide solution andsaturated saline solution, and dried over magnesium sulfate. The solventis concentrated and the resulting residue is purified by silica gelcolumn chromatography (eluent; chloroform: methanol=500:1), andrecrystallized from ethanol to give1-{4-[2-(6-acetyloxyhexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(1.07 g) as white powder, m.p. 145°-146° C.

Using the suitable starting materials, the compound of the above Example360 is obtained in the same manner as in Example 396.

EXAMPLE 397

A mixture of1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g), diethylamine (0.16 ml), triethylamine (0.21 ml) andacetonitrile (20 ml) is refluxed overnight. The solvent is distilled offand the resulting residue is dissolved in chloroform, washedsuccessively with water and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is purified by silica gel column chromatography (eluent;chloroform:methanol=200:1→50:1) and converted into the hydrochloridethereof in methanol. The product is recrystallized from methanol/diethylether to give1-{4-[2-(6-diethylaminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride (0.42 g) as white powder, m.p. 91°-95° C.

Using the suitable starting materials, the compounds of the aboveExamples 330, 332, 333, 335, 336, 339, 341, 342, 344-349, 352-355, 357and 366 are obtained in the same manner as in Example 397.

EXAMPLE 398

A mixture of1-{4-[2-(6-bromohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(4.00 g), potassium phthalimide (2.02 g) and dimethylformamide (100 ml)is stirred at 100° C. for 5 hours. The reaction mixture is filtered andthe filtrate is distilled off. The resulting residue is extracted withethyl acetate and the organic layer is washed successively with waterand saturated saline solution, and dried over magnesium sulfate. Thesolvent is distilled off and the resulting residue is purified by silicagel column chromatography (eluent; dichloromethane), and recrystallizedfrom methanol/diethyl ether to givet-{4-[2-(6-phthalimidohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(4.06 g) as white powder, m.p. 145°-146.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 331, 340, 364 and 365 are obtained in the same manner as inExample 398.

EXAMPLE 399

A mixture of1-{4-[2-[6-phthalimidohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(3.75 g), hydrazine hydrate (0.44 ml) and ethanol (30 ml) is refluxedfor 3.5 hours. The precipitated crystal is collected by filtration,dried and purified by silica gel column chromatography (eluent;chloroform:methanol:aqueous ammonia=100:10:1), and recrystallized frommethanol/diethyl ether to give1-{4-[2-(6-aminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(2.52 g) as white powder, m.p. 135.5°-137.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 284, 344 and 345 are obtained in the same manner as in Example399.

EXAMPLE 400

A mixture of1-{4-[2-(6-aminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g), acetic anhydride (20 ml) and two drops of conc. sulfuric acidis stirred at room temperature for 3 hours. To the reaction mixture isadded aqueous 2N aqueous sodium hydroxide solution under ice-cooling andthe mixture is extracted with chloroform. The organic layer is washedsuccessively with water and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is purified by silica gel column chromatography (eluent;chloroform:methanol=200:1), and recrystallized from methanol/diethylether to give1-{4-[2-(6-acetylaminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.60 g) as colorless needles, m.p. 171°-172° C.

EXAMPLE 401

A mixture of1-{4-[2-(6-aminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g), benzoyl chloride (0.20 ml), triethylamine and dichloromethane(20 ml) is stirred at room temperature for 1 hour. The reaction mixtureis washed successively with water and saturated saline solution, anddried over magnesium sulfate. The solvent is concentrated and theresulting residue is recrystallized from ethanol to give1-{4-[2-(6-benzoylaminohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine(0.71 g) as white powder, m.p. 178°-178.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 348 and 357 are obtained in the same manner as in Examples 400and 401.

EXAMPLE 402

A mixture of1-[4-(2-ethoxycarbonylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.00 g), aqueous ammonia (100 ml), ammonium chloride (0.3 g) andmethanol (150 ml) is heated at 100° C. for 4 hours in a sealed tube. Thesolvent is distilled off and the resulting residue is extracted withchloroform, washed successively with water and saturated salinesolution, and dried over magnesium sulfate. The solvent is concentratedand the resulting residue is purified by silica gel columnchromatography (eluent; chloroform:methanol=50:1), and recrystallizedfrom methanol/diethyl ether to give1-[4-(2-carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.43 g) as white powder, m.p. 198°-199° C.

EXAMPLE 403

A mixture of1-[4-(2-chloro-4-aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g), acetic anhydride (15 ml), acetic acid (5 ml) and a drop ofsulfuric acid is stirred at room temperature for 1 hour. To the reactionmixture is added aqueous 2N aqueous sodium hydroxide solution and themixture is extracted with chloroform. The extract is washed withsaturated saline solution and dried over magnesium sulfate. The solventis concentrated and the resulting residue is recrystallized frommethanol/diethyl ether to give1-[4-(2-chloro-4-acetylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.28 g) as white powder, m.p. 214°-243° C.

Using the suitable starting materials, the compound of the above Example44 is obtained in the same manner as in Example 403.

EXAMPLE 404

A mixture of1-[4-(1-benzyloxycarbonyl-4-piperidinylcarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(8.00 g), 10% Pd-C (0.8 g) and ethanol (250 ml) is subjected tocatalytic hydrogenation at 50° C. under 4 atm. of hydrogen pressure for6 hours. The catalyst is removed by filtration and the liltrate isevaporated under reduced pressure. The resulting residue is extractedwith ethyl acetate and washed successively with water and saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified by silica gel columnchromatography (eluent; chloroform: methanol: ammoniumhydroxide=50:10:1) to give1-{4-[4-(4-piperidinyl)benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(4.80 g), and a part (0.5 g) thereof is converted into the hydrochloridethereof in methanol. The hydrochloride is recrystallized frommethanol/diethyl ether to give1-{4-[4-(4-piperidinyl)benzoylamino]benzoyl)-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride (0.42 g) as white powder, m.p. 177°-181.5° C.

EXAMPLE 405

Using the suitable starting materials, the following compound isobtained in the same manner as in the above Examples 1, 382 and 388.

1-[4-(4-Dimethylaminobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline,colorless amorphous

¹ H-NMR (DMSO-d₆) δ: 1.90-2.00 (2H, m), 2.82 (2H, t, J=6.5 Hz), 2.98(6H, s), 3.77 (2H, t, J=6.5 Hz), 6.70-7.30 (6H, m), 7.32 (2H, d, J=8.6Hz), 7.73 (2H, d, J=8.6 Hz), 8.00-8.20 (1H, m), 8.39 (1H, d, J=2.2 Hz),10.37 (1H, s)

Using the suitable starting materials, the following compounds areobtained in the same manner as in Example 1. ##STR462##

EXAMPLE 406 ##STR463## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 216°-218° C. Form: Free EXAMPLE 407##STR464## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 181°-183° C. Form: Free EXAMPLE 408 ##STR465##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 207°-208° C. Form: Free EXAMPLE 409 ##STR466##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 213°-214° C. Form: Free EXAMPLE 410 ##STR467##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 136°-138° C. Form: Free EXAMPLE 411 ##STR468##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 130°-132° C. Form: Free EXAMPLE 412 ##STR469##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 143°-145° C. Form: Free EXAMPLE 413 ##STR470##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 171°-173° C. Form: Free EXAMPLE 414 ##STR471##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 162°-164° C. Form: Free EXAMPLE 415 ##STR472##Crystalline form: Colorless amorphous NMR analysis: 49) Form: FreeEXAMPLE 416 ##STR473## Crystalline form: Colorless amorphous NMRanalysis: 50) Form: Free EXAMPLE 417 ##STR474## Crystalline form:Colorless amorphous NMR analysis: 51) Form: Free EXAMPLE 418 ##STR475##Crystalline form: Colorless needles Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 228.5°-230° C. Form: Free EXAMPLE 419##STR476## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 205.5°-206.5° C. Form: FreeEXAMPLE 420 ##STR477## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 210°-212° C. Form: FreeEXAMPLE 421 ##STR478## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 166°-167° C. Form: Free EXAMPLE 422##STR479## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 191.5°-192.5° C. Form: Free EXAMPLE 423##STR480## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 209°-210° C. Form: Free EXAMPLE 424 ##STR481##Crystalline form: Colorless amorphous NMR analysis: 52) Form: FreeEXAMPLE 425 ##STR482## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 148°-149° C. Form: Free EXAMPLE 426##STR483## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 157°-158° C. Form: Free EXAMPLE 427 ##STR484##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 194.5°-195.5° C. Form: Free EXAMPLE 428 ##STR485##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 179.5°-180.5° C. Form: Free EXAMPLE 429 ##STR486##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 190°-191° C. Form: Free EXAMPLE 430 ##STR487##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 159°-160° C. Form: Free EXAMPLE 431 ##STR488##Crystalline form: Colorless amorphous NMR analysis: 53) Form:Hydrochloride EXAMPLE 432 ##STR489## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 155°-156° C. Form:Free EXAMPLE 433 ##STR490## Crystalline form: Colorless amorphous NMRanalysis: 54) Form: Free EXAMPLE 434 ##STR491## Crystalline form:Colorless amorphous NMR analysis: 55) Form: Free EXAMPLE 435 ##STR492##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 175°-177° C. Form: Free EXAMPLE 436 ##STR493##Crystalline form: Colorless amorphous NMR analysis: 56) Form: FreeEXAMPLE 437 ##STR494## Crystalline form: Colorless amorphous NMRanalysis: 57) Form: Free EXAMPLE 438 ##STR495## Crystalline form: Whitepowder Recrystallization solvent: Dichloromethane/diethyl ether MeltingPoint: 219°-220° C. Form: Free EXAMPLE 439 ##STR496## Crystalline form:White powder Recrystallization solvent: Dichloromethane/diethyl etherMelting Point: 215°-218° C. Form: Free EXAMPLE 440 ##STR497##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 128.5°-129.5° C. Form: Free EXAMPLE 441 ##STR498##Crystalline form: Colorless amorphous NMR analysis: 58) Form: FreeEXAMPLE 442 ##STR499## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 153°-154° C. Form: Free EXAMPLE 443##STR500## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 150°-153° C. Form: Free EXAMPLE 444 ##STR501##Crystalline form: White powder Recrystallization solvent: EthanolMelting Point: 139°-141° C. Form: Free EXAMPLE 445 ##STR502##Crystalline form: Colorless amorphous NMR analysis: 59) Form: FreeEXAMPLE 446 ##STR503## Crystalline form: Colorless amorphous NMRanalysis: 60) Form: Free EXAMPLE 447 ##STR504## Crystalline form:Colorless amorphous NMR analysis: 61) Form: Free EXAMPLE 448 ##STR505##Crystalline form: Colorless amorphous NMR analysis: 62) Form: FreeEXAMPLE 449 ##STR506## Crystalline form: Colorless amorphous NMRanalysis: 63) Form: Free EXAMPLE 450 ##STR507## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:172.5°-173.5° C. Form: Free EXAMPLE 451 ##STR508## Crystalline form:Colorless prisms Recrystallization solvent: Methanol/diethyl etherMelting Point: 122.5°-123° C. Form: Free EXAMPLE 452 ##STR509##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 198°-199.5° C. Form: Free EXAMPLE453 ##STR510## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 118°-119.5° C. Form: HydrochlorideEXAMPLE 454 ##STR511## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 163°-165° C. Form: DihydrochlorideEXAMPLE 455 ##STR512## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 246°-248° C. Form:Hydrochloride EXAMPLE 456 ##STR513## Crystalline form: White powderRecrystallization solvent: Chloroform/ethanol Melting Point: 204°-205°C. Form: Free EXAMPLE 457 ##STR514## Crystalline form: Colorless prismsRecrystallization solvent: Methanol/diethyl ether Melting Point:127°-128° C. Form: Hydrochloride EXAMPLE 458 ##STR515## Crystallineform: White powder Recrystallization solvent: Methanol/diethyl etherMelting Point: 220°-221° C. Form: Free EXAMPLE 459 ##STR516##Crystalline form: Colorless needles Recrystallization solvent: EthanolMelting Point: 190°-192° C. Form: Free EXAMPLE 460 ##STR517##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 189°-191° C. Form: HydrochlorideEXAMPLE 461 ##STR518## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol Melting Point: 173°-174° C. Form:Free EXAMPLE 462 ##STR519## Crystalline form: White powderRecrystallization solvent: Dichloromethane/ethanol Melting Point:129°-130° C. Form: Free EXAMPLE 463 ##STR520## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:130°-133° C. Form: Hydrochloride EXAMPLE 464 ##STR521## Crystallineform: Light yellow powder Recrystallization solvent: Methanol/diethylether Melting Point: 170.5°-172° C. Form: Hydrochloride EXAMPLE 465##STR522## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 126°-131° C. Form: HydrochlorideEXAMPLE 466 ##STR523## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 182°-185° C. Form: DihydrochlorideEXAMPLE 467 ##STR524## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 116°-121° C. Form:Hydrochloride EXAMPLE 468 ##STR525## Crystalline form: Colorless prismsRecrystallization solvent: Methanol/diethyl ether Melting Point:178°-182.5° C. Form: Free EXAMPLE 469 ##STR526## Crystalline form:Colorless particles Recrystallization solvent: Methanol/diethyl etherMelting Point: 185°-187° C. Form: Free EXAMPLE 470 ##STR527##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 215°-217° C. Form: Free EXAMPLE471 ##STR528## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 176°-178° C. Form: Free EXAMPLE472 ##STR529## Crystalline form: Light yellow powder Recrystallizationsolvent: Methanol/n-hexane Melting Point: 194.5°-197° C. Form: FreeEXAMPLE 473 ##STR530## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 161.5°-165.5° C. Form:Hydrochloride EXAMPLE 474 ##STR531## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 152°-153° C.Form: Free EXAMPLE 475 ##STR532## Crystalline form: Colorless needlesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:147°-148° C. Form: Free EXAMPLE 476 ##STR533## Crystalline form: Lightyellow powder Recrystallization solvent: Ethyl acetate Melting Point:215°-217° C. Form: Free EXAMPLE 477 ##STR534## Crystalline form:Colorless amorphous NMR analysis: 64) Form: Free EXAMPLE 478 ##STR535##Crystalline form: White powder Recrystallization solvent: Ethyl acetateMelting Point: 180°-181° C. Form: Free EXAMPLE 479 ##STR536##Crystalline form: Colorless amorphous NMR analysis: 65) Form: FreeEXAMPLE 480 ##STR537## Crystalline form: Colorless amorphous NMRanalysis: 66) Form: Free EXAMPLE 481 ##STR538## Crystalline form:Colorless amorphous NMR analysis: 67) Form: Free EXAMPLE 482 ##STR539##Crystalline form: Colorless scales Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 165°-167° C. Form: Free EXAMPLE483 ##STR540## Crystalline form: Colorless amorphous NMR analysis: 68)Form: Free EXAMPLE 484 ##STR541## Crystalline form: Colorless amorphousNMR analysis: 69) Form: Free EXAMPLE 485 ##STR542## Crystalline form:Colorless amorphous NMR analysis: 70) Form: Free EXAMPLE 486 ##STR543##Crystalline form: Colorless amorphous NMR analysis: 71) Form: FreeEXAMPLE 487 ##STR544## Crystalline form: Colorless amorphous NMRanalysis: 72) Form: Free EXAMPLE 488 ##STR545## Crystalline form:Colorless amorphous NMR analysis: 73) Form: Free EXAMPLE 489 ##STR546##Crystalline form: Light yellow amorphous NMR analysis: 74) Form: FreeEXAMPLE 490 ##STR547## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate Melting Point: 182°-182.5° C. Form: Free EXAMPLE491 ##STR548## Crystalline form: White powder Recrystallization solvent:Ethyl acetate Melting Point: 244°-245° C. Form: Free EXAMPLE 492##STR549## Crystalline form: White powder Recrystallization solvent:Ethyl acetate Melting Point: 220°-221.5° C. Form: Free EXAMPLE 493##STR550## Crystalline form: Light yellow amorphous NMR analysis: 75)Form: Free EXAMPLE 494 ##STR551## Crystalline form: Light yellowamorphous NMR analysis: 76) Form: Free EXAMPLE 495 ##STR552##Crystalline form: Colorless needles Recrystallization solvent:Methanol/diethyl ether Melting Point: 171°-172° C. Form: Free EXAMPLE496 ##STR553## Crystalline form: White powder Recrystallization solvent:Ethanol Melting Point: 178°-178.5° C. Form: Free EXAMPLE 497 ##STR554##EXAMPLE 498 ##STR555## EXAMPLE 499 ##STR556## EXAMPLE 500 ##STR557##EXAMPLE 501 ##STR558## EXAMPLE 502 ##STR559## EXAMPLE 503 ##STR560##EXAMPLE 504 ##STR561## Crystalline form: Light yellow scalesRecrystallization solvent: Ethanol/water Melting Point: 129°-131° C.Form: Free EXAMPLE 505 ##STR562## Crystalline form: White powderRecrystallization solvent: Ethyl acetate Melting Point: 199°-201° C.Form: Free EXAMPLE 506 ##STR563## Crystalline form: Colorless amorphousNMR analysis: 77) Form: Free EXAMPLE 507 ##STR564## Crystalline form:White powder Recrystallization solvent: n-Hexane/ethyl acetate MeltingPoint: 187.5°-189° C. Form: Free EXAMPLE 508 ##STR565## Crystallineform: White powder Recrystallization solvent: Methanol/diethyl etherMelting Point: 161°-164° C. Form: Free EXAMPLE 509 ##STR566##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 242°-243° C. Form: Free EXAMPLE 510 ##STR567##Crystalline form: White powder Recrystallization solvent:Dichloroethane/diethyl ether Melting Point: 186°-188° C. Form: FreeEXAMPLE 511 ##STR568## Crystalline form: Colorless amorphous NMRanalysis: 78) Form: Free EXAMPLE 512 ##STR569## Crystalline form:Colorless amorphous NMR analysis: 79) Form: Free

49) ¹ H-NMR(CDCl₃) δ; 1.11 (3H, t, J=7.1 Hz), 1.90-2.25 (2H, m), 2.29(3H, s), 2.55 (2H, q, J=7.1 Hz), 3.62-3.90 (2H, m), 4.00-4.20 (1H, m),6.63 (1H, d, J=7.9 Hz), 6.85-7.10 (2H, m), 7.25-7.80 (9H, m), 8.25 (1H,brs)

50) ¹ H-NMR(CDCl₃) δ; 1.10 (3H, t, J=7.1 Hz), 1.90-2.20 (2H, m), 2.28(3H, s), 3.60-3.90 (2H, m), 3.95-4.20 (1H, m), 6.62 (1H, d, J=7.9 Hz),6.80-7.10 (2H, m), 7.20 (2H, d, J=8.6 Hz), 7.31-7.55 (4H, m), 7.80 (2H,d, J=1.9 Hz), 9.05 (1H, brs)

51) ¹ H-NMR(CDCl₃) δ; 1.80-2.05 (1H, m), 2.15-2.50 (1H, m), 2.34 (6H,s), 2.51 (3H, s), 3.48-3.62 (1H, m), 3.72 (3H, s), 3.70-3.85 (1H, m),4.00-4.22 (1H, m), 6.64 (1H, d, J=7.8 Hz), 6.84-7.58 (9H, m), 8.16 (1H,brs), 8.40 (1H, d, J=8.7 Hz)

52) ¹ H-NMR(CDCl₃) δ; 1.16 (3H, t, J=7.1 Hz), 2.40-2.70 (2H, m),2.90-3.30 (3H, m), 3.80-4.20 (2H, m), 4.80-5.00 (1H, m), 6.60-6.80 (1H,m), 7.00-7.70 (10H, m), 8.24 (1H, s)

53) ¹ H-NMR (DMSO-d₆) δ; 1.0-2.5 (10H, m), 2.34 (3H, s), 3.30-3.80 (4H,m), 4.50-5.30 (3H, m), 6.70-7.00 (1H, m), 7.10-7.80 (11H, m), 10.43 (1H,s), 10.5-12.0 (1H, br)

54) ¹ H-NMR(CDCl₃) δ; 1.10-2.10 (10H, m), 2.40-2.70 (1H, m), 2.80-3.20(3H, m), 3.92 (2H, s), 4.90-5.20 (1H, m), 6.50-6.70 (1H, m), 6.80-7.60(8H, m), 7.75 (2H, s), 8.73 (1H, s)

55) ¹ H-NMR(CDCl₃) δ; 1.10-2.20 (10H, m), 2.40-2.70 (1H, m), 2.90-3.30(3H, m), 3.93 (2H, s), 4.90-5.20 (1H, m), 6.62 (1H, d, J=7.6 Hz),6.90-7.70 (10H, m), 8.29 (1H, s)

56) ¹ H-NMR(CDCl₃) δ; 1.50-2.10 (2H, m), 2.38 (6H, s), 2.30-2.70 (1H,m), 2.70-3.00 (2H, m), 3.45 (1H, d, J=13 Hz), 3.81 (1H, d, J=14 Hz),4.70-5.00 (1H, m), 7.0-7.50 (12H, m), 8.23 (1H, s)

57) ¹ H-NMR(CDCl₃) δ; 1.50-2.10 (2H, 7) m), 2.42 (3H, s), 2.40-2.70 (1H,m), 2.80-3.00 (2H, m), 3.52 (1H, d, J=13 Hz), 3.85 (1H, d, J=13 Hz),4.70-5.00 (1H, m), 7.00-7.70 (12H, m), 8.54 (1H, s)

58) ¹ H-NMR(CDCl₃) δ; 2.43 (3H, s), 2.47 (3H, s), 3.00-3.30 (3H, m),3.76 (1H, d, J=14 Hz), 4.06 (1H, d, J=14 Hz), 4.90-5.20 (1H, m),6.50-6.80 (3H, m), 6.90-7.50 (6H, m), 7.70-8.00 (2H, m), 8.48 (1H, d,J=8 Hz), 10.58 (1H, s)

59) ¹ H-NMR(CDCl₃) δ; 2.41 (3H, s), 2.44 (3H, s), 2.90-3.20 (3H, m),3.74 (1H, d, J=13 Hz), 4.07 (1H, d, J=14 Hz), 4.80-5.00 (1H, m), 6.67(1H, d, J=7 Hz), 6.76 (1H, d, J=7 Hz), 7.00-7.50 (8H, m), 7.55 (1H, s),7.70-7.90 (2H, m)

60) ¹ H-NMR(CDCl₃) δ; 2.41 (3H, s), 2.80-3.20 (3H, m), 3.73 (1H, d, J=13Hz), 4.03 (1H, d, J=14 Hz), 6.66 (2H, d, J=7.6 Hz), 6.90-8.00 (10H, m),8.57 (1H, s)

61) ¹ H-NMR (CDCl₃) δ; 2.40 (3H, s), 2.90-3.20 (3H, m), 3.73 (1H, d,J=13 Hz), 4.07 (1H, d, J=13 Hz), 4.70-5.00 (1H, m), 6.60-6.80 (2H, m),6.90-8.00 (10H, m), 8.54 (1H, s)

62) ¹ H-NMR (CDCl₃) δ; 2.41 (3H, s), 2.90-3.20 (3H, m), 3.75 (1H, d,J=14 Hz), 4.08 (1H, d, J=14 Hz), 4.80-5.00 (1H, m), 6.67 (1H, d, J=7.6Hz), 6.82 (1H, d, J=7.6 Hz), 6.90-7.90 (10H, m), 8.08 (1H, s)

63) ¹ H-NMR(CDCl₃) δ; 1.23 (3H, t, J=7 Hz), 1.40-1.70 (1H, m), 1.90-2.20(3H, m), 2.70-3.30 (3H, m), 3.40-3.60 (5H, m), 3.91 (2H, s), 5.00-5.20(1H, m), 6.60-7.40 (11H, m), 8.12 (1H, d, J=8 Hz), 8.99 (1H, s)

64) ¹ H-NMR (CDCl₃) δ; 1.35-1.70 (1H, m), 1.80-2.20 (3H, m), 2.25-2.35(1H, m), 2.65-3.20 (3H, m), 4.01 (2H, s), 4.05-4.17 (2H, m), 4.90-5.10(1H, m), 6.61 (1H, d, J=7.5 Hz), 6.75-7.50 (12H, m), 8.44 (1H, brs)

65) ¹ H-NMR(CDCl₃) δ; 1.13 (3H, t, J=7.0 Hz), 1.30-1.65 (4H, m),1.80-2.20 (3H, m), 2.28 (3H, s), 2.65-3.40 (5H, m), 4.90-5.10 (1H, m),6.63 (1H, d, J=7.8 Hz), 6.75-7.00 (3H, m), 7.00-7.45 (8H, m), 8.85 (1H,brs)

66) ¹ H-NMR(CDCl₃) δ; 0.88 (3H, t, J=7.4 Hz), 1.16 (3H, t, J=7.0 Hz),1.35-2.20 (6H, m), 2.27 (3H, s), 2.60-3.20 (3H, m), 3.20-3.45 (2H, m),3.85-4.10 (1H, m), 4.90-5.10 (1H, m), 6.63 (1H, d, J=7.4 Hz), 6.77 (2H,d, J=8.5 Hz), 6.92 (1H, t, J=8.0 Hz), 7.00-7.45 (8H, m), 8.85 (1H, brs)

67) ¹ H-NMR(CDCl₃) δ; 1.17 (3H, t, J=7.0 Hz), 1.35-1.65 (4H, m),2.60-3.45 (5H, m), 4.20 (2H, q, J=7.0 Hz), 4.90-5.10 (1H, m), 6.63 (1H,d, J=7.6 Hz), 6.80-7.45 (12H, m), 8.66 (1H, brs)

68) ¹ H-NMR(CDCl₃) δ; 0.96 (6H, d, J=6.6 Hz), 1.35-1.65 (1H, m),1.80-2.25 (4H, m), 2.65-3.15 (3H, m), 3.19 (2H, d, J=7.3 Hz), 3.99 (2H,s), 4.90-5.10 (1H, m), 6.60 (1H, d, J=7.8 Hz), 6.75-7.05 (4H, m),7.05-7.40 (8H, m), 8.15 (1H, brs)

69) ¹ H-NMR(CDCl₃) δ; 1.19 (3H, t, J=7.0 Hz), 1.35-1.65 (1H, m),1.80-2.25 (3H, m), 2.70-3.20 (3H, m), 3.44 (2H, q, J=7.0 Hz), 3.77 (3H,s), 3.87 (2H, s), 4.90-5.10 (1H, m), 6.25-6.50 (3H, m), 6.67 (1H, d,J=7.5 Hz), 6.85-7.45 (8H, m), 8.29 (1H, brs)

70) ¹ H-NMR(CDCl₃) δ; 1.05 (3H, t, J=7.1 Hz), 1.35-1.65 (1H, m),1.85-2.25 (3H, m), 2.65-3.30 (5H, m), 3.74 (2H, s), 4.95-5.15 (1H, m),6.63 (1H, d, J=7.5 Hz), 6.80-7.55 (11H, m), 9.51 (1H, brs)

71) ¹ H-NMR(CDCl₃) δ; 1.30-1.65 (1H, m), 1.80-2.30 (3H, m), 2.65-3.15(3H, m), 3.75 (2H, s), 3.74 (2H, s), 4.95-5.10 (1H, m), 6.45-6.70 (3H,m), 6.88 (1H, t, J=6.8 Hz), 7.00-7.45 (8H, m), 8.74 (1H, brs)

72) ¹ H-NMR(CDCl₃) δ; 1.30-1.70 (1H, m), 1.75-2.25 (6H, m), 2.65-3.15(3H, m), 3.78 (2H, d, J=5.4 Hz), 4.28 (2H, d, J=5.5 Hz), 4.53 (1H, brs),4.90-5.10 (1H, m), 5.89 (1H, brs), 6.50-6.70 (3H, m), 6.89 (1H, t, J=7.5Hz), 7.00-7.40 (8H, m), 8.61 (1H, brs)

73) ¹ H-NMR (CDCl₃) δ; 1.35-1.65 (1H, m), 1.70-2.20 (8H, m), 2.65-3.20(3H, m), 3.25-3.55 (4H, m), 3.88 (2H, s), 4.90-5.10 (1H, m), 5.79 (1H,brs), 6.55-7.40 (13H, m), 8.37 (1H, brs)

74) ¹ H-NMR (CDCl₃) δ; 1.35-2.00 (8H, m), 2.65-3.20 (3H, m), 3.30-3.35(2H, m), 3.60-3.85 (2H, m), 3.90 (2H, s), 4.95-5.15 (1H, m), 6.55-7.00(5H, m), 7.00-7.40 (8H, m), 7.65-7.90 (4H, m), 8.22 (1H, brs)

75) ¹ H-NMR (CDCl₃) δ; 1.16 (3H, t, J=7.0 Hz), 2.39 (3H, s), 2.80-3.20(3H, m), 3.44 (2H, q, J=7.0 Hz), 3.65-4.20 (4H, m), 4.80-5.05 (1H, m),6.50-7.45 (13H, m), 8.50 (1H, brs)

76) ¹ H-NMR (CDCl₃) δ; 1.23 (3H, t, J=7.0 Hz), 2.41 (3H, s), 2.75-3.20(3H, m), 3.40-3.60 (5H, m), 3.65-3.90 (1H, m), 3.92 (2H, s), 3.90-4.20(1H, m), 4.85-5.10 (1H, m), 6.65-7.45 (11H, m), 8.13 (1H, d, J=8.4 Hz),9.01 (1H, brs)

77) ¹ H-NMR (CDCl₃) δ; 1.80-1.95 (1H, m), 2.20-2.70 (10H, m), 3.50-3.60(1H, m), 3.63-3.80 (1H, m), 4.00-4.15 (1H, m), 6.60 (1H, d, J=7.6 Hz),6.92 (1H, t, J=7.6 Hz), 7.02 (1H, t, J=6.3 Hz), 7.20-7.65 (9H, m), 7.87(1H, brs)

78) ¹ H-NMR (CDCl₃) δ; 1.40-1.62 (1H, m), 1.84-2.22 (3H, m), 2.65-3.19(3H, m), 3.97 (2H, t, J=4.9 Hz), 4.43 (2H, t, J=4.9 Hz), 4.95-5.18 (1H,m), 6.60-6.77 (1H, m), 6.85-7.02 (2H, m), 7.02-7.30 (5H, m), 7.40-7.68(3H, m), 8.20-8.32 (1H, m), 9.62-9.81 (1H, m)

79) ¹ H-NMR (CDCl₃) δ; 1.38-1.65 (1H, m), 1.84-2.21 (3H, m), 2.64-3.15(3H, m), 3.81 (2H, t, J=5.7 Hz), 4.25 (2H, t, J=5.7 Hz), 4.90-5.13 (1H,m), 6.58-6.71 (1H, m), 6.82-7.00 (1H, m), 7.00-7.52 (10H, m), 8.11 (1H,brs)

EXAMPLE 513

To a solution of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(1.06 g) in dichloromethane (80 ml) is added o-methylphenyl isocyanate(0.66 g) under ice-cooling. The mixture is stirred at room temperaturefor 4 hours. After completion of the reaction, the solvent isconcentrated under reduced pressure and the resulting residue ispurified by silica gel column chromatography (eluent; n-hexane:ethylacetate=1:1), and recrystallized from ethyl acetate to give1-[4-(2-methylanilinocarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.97 g) as white powder, m.p. 182°-182.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 491°-492 are obtained in the same manner as in Example 513.

EXAMPLE 514

A mixture of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.50g), phenylsulfonyl chloride (0.29 ml), triethylamine (0.32 ml) anddichloromethane (30 ml) is stirred at room temperature overnight. Thereaction mixture is washed successively with water and saturated salinesolution, and dried over magnesium sulfate. The solvent is distilled offand the resulting residue is purified by silica gel columnchromatography (eluent; chloroform), and recrystallized frommethanol/diethyl ether to give1-(4-phenylsulfonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.27g) as colorless prisms, m.p. 178°-182.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 469-471, 498, 502 and 503 are obtained in the same manner as inExample 514.

EXAMPLE 515

To a solution of1-[4-(4-piperidinylcarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) in dimethylformamide (20 ml) is added 60% sodium hydridedispersion in mineral oil (82 mg) and the mixture is stirred at roomtemperature for 30 minutes. Thereto is added methyl iodide (0.14 ml) andthe mixture is stirred at room temperature overnight. The solvent isdistilled off and the resulting residue is extracted with chloroform,and washed successively with water and saturated saline solution, anddried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; chloroform:methanol=10:1), and recrystallized frommethanol/n-hexane to give1-{4-[N-(1-methyl-4-piperidinylcarbonyl)-N-methylamino]benzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(0.03 g) as light yellow powder, m.p. 194.5°-197° C.

Using the suitable starting materials, the compounds of the aboveExamples 497 and 501 are obtained in the same manner as in Example 515.

EXAMPLE 516

6-Fluoro-1-(4-aminobenzoyl)-1,2,3,4-tetrahydroquinoline (0.15 g) isdissolved in dichloromethane (10 ml) and thereto is added triethylamine(0.31 ml). To the mixture is added dropwise a solution of3,5-dichlorobenzoyl chloride (0.14 g) in dichloromethane (2.0 ml) underice-cooling, and the mixture is stirred for 30 minutes underice-cooling, and further, at room temperature for 1 hour. To the mixtureare added triethylamine (0.31 ml) and 3,5-dichlorobenzoyl chloride (0.14ml). The mixture is stirred at room temperature for 4 hours. Thereaction mixture is washed with water, and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent; ethylacetate:n-hexane=1:5→1:4), and recrystallized from ethylacetate/n-hexane to give6-fluoro-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline(0.12 g) and6-fluoro-1-(4-[bis-(3,5-dichlorobenzoyl)amino]-benzoyl}-1,2,3,4-tetrahydroquinoline.

The former: White powder, m.p. 205.5°-206.5° C.

The latter: White powder, m.p. 210.5°-212° C.

EXAMPLE 517

Using the suitable starting materials, the compounds of the aboveExamples 450 and 504 are obtained in the same manner as in Example 378.

EXAMPLE 518

Using the suitable starting materials, the compounds of the aboveExamples 450-467, 495, 496, 499, 500, 511 and 512 are obtained in thesame manner as in Example 380.

EXAMPLE 519

Using the suitable starting materials, the compounds of the aboveExamples 449, 474-489, 493 and 494 are obtained in the same manner as inExample 394.

EXAMPLE 520

Using the suitable starting materials, the compounds of the aboveExamples 453, 455, 457, 459, 460, 463-467, 495, 496 and 499 are obtainedin the same manner as in Example 397.

EXAMPLE 521

Using the suitable starting materials, the compound of the above Example461 is obtained in the same manner as in Example 396.

EXAMPLE 522

Using the suitable starting materials, the compound of the above Example456 is obtained in the same manner as in Example 398.

EXAMPLE 523

Using the suitable starting materials, the compound of the above Example459 is obtained in the same manner as in Example 399.

EXAMPLE 524

Using the suitable starting materials, the compounds of the aboveExamples 495 and 496 are obtained in the same manner as in Examples 400and 401.

EXAMPLE 525

Using the suitable starting materials, the compound of the above Example458 is obtained in the same manner as in Example 402.

Using the suitable starting materials, the compounds of the followingTable 3 are obtained in the same manner as in Examples 1 and 382.##STR570##

EXAMPLE 527 ##STR571## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 225°-226° C. Form: FreeEXAMPLE 528 ##STR572## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 142.5°-145° C. Form: FreeEXAMPLE 529 ##STR573## Crystalline form: White powder Recrystallizationsolvent Methanol/diethyl ether Melting Point: 213°-215° C. Form: FreeEXAMPLE 530 ##STR574## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 167°-167.5° C. Form: FreeEXAMPLE 531 ##STR575## Crystalline form: Colorless scalesRecrystallization solvent: Methanol/diethyl ether Melting Point:217°-221° C. Form: Free EXAMPLE 532 ##STR576## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:182°-184° C. Form: Free EXAMPLE 533 ##STR577## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:209°-210° C. Form: Free EXAMPLE 534 ##STR578## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:148°-149° C. Form: Free EXAMPLE 535 ##STR579## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:202°-203° C. Form: Free EXAMPLE 536 ##STR580## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:218°-219° C. Form: Free EXAMPLE 537 ##STR581## Crystalline form: Whitepowder Recrystallization solvent: Methanol/n-hexane Melting Point:159°-160° C. Form: Free EXAMPLE 538 ##STR582## Crystalline form: Whitepowder Recrystallization solvent: Methanol/n-hexane Melting Point:201°-202° C. Form: Free EXAMPLE 539 ##STR583## Crystalline form: Whitepowder Recrystallization solvent: Methanol/n-hexane Melting Point:205°-207° C. Form: Free EXAMPLE 540 ##STR584## Crystalline form: Whitepowder Recrystallization solvent: Methanol/diethyl ether Melting Point:201.5°-202.5° C. Form: Free EXAMPLE 541 ##STR585## Crystalline form:White powder Recrystallization solvent: Methanol/diethyl ether MeltingPoint: 226°-228° C. Form: Free EXAMPLE 542 ##STR586## Crystalline form:White powder Recrystallization solvent: Methanol/diethyl ether MeltingPoint: 218°-221° C. Form: Free EXAMPLE 543 ##STR587## Crystalline form:White powder Recrystallization solvent: Methanol/diethyl ether MeltingPoint: 156°-157° C. Form: Free EXAMPLE 544 ##STR588## Crystalline form:White powder NMR analysis: 80) Form: Free EXAMPLE 545 ##STR589##Crystalline form: Colorless amorphous NMR analysis: 81) Form: FreeEXAMPLE 546 ##STR590## Crystalline form: Colorless amorphous NMRanalysis: 82) Form: Free EXAMPLE 547 ##STR591## Crystalline form: Lightyellow amorphous NMR analysis: 83) Form: Free EXAMPLE 548 ##STR592##Crystalline form: Colorless amorphous NMR analysis: 84) Form: FreeEXAMPLE 549 ##STR593## Crystalline form: Colorless amorphous NMRanalysis: 85) Form: Free EXAMPLE 550 ##STR594## Crystalline form: Whitepowder Recrystallization solvent: n-Hexane/ethyl acetate Melting Point:135°-136° C. Form: Free EXAMPLE 551 ##STR595## Crystalline form:Colorless prisms Recrystallization solvent: n-Hexane/ethyl acetateMelting Point: 122°-123° C. Form: Free EXAMPLE 552 ##STR596##Crystalline form: Colorless prisms Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 118°-119° C. Form: Free EXAMPLE553 ##STR597## Crystalline form: Colorless prisms Recrystallizationsolvent: n-Hexane/ethyl acetate Melting Point: 145°-147° C. Form: FreeEXAMPLE 554 ##STR598## Crystalline form: Light yellow needlesRecrystallization solvent: n-Hexane/ethyl acetate Melting Point:169.5°-170.5° C. Form: Free EXAMPLE 555 ##STR599## Crystalline form:Colorless prisms Recrystallization solvent: n-Hexane/ethyl acetateMelting Point: 194°-195° C. Form: Free EXAMPLE 556 ##STR600##Crystalline form: Colorless needles Recrystallization solvent:n-Hexane/ethyl acetate Melting Point: 202°-204° C. Form: Free EXAMPLE557 ##STR601## Crystalline form: Colorless prisms Recrystallizationsolvent: Ethanol Melting Point: 242°-243° C. Form: Free EXAMPLE 558##STR602## Crystalline form: Light yellow powder NMR analysis: 86) Form:Free EXAMPLE 559 ##STR603## Crystalline form: Light yellow powder NMRanalysis: 87) Form: Free EXAMPLE 560 ##STR604## Crystalline form:Colorless needles Recrystallization solvent: Ethanol Melting Point:237°-238° C. Form: Free EXAMPLE 561 ##STR605## Crystalline form:Colorless prisms Recrystallization solvent: Dioxane Melting Point:258°-259° C. Form: Free EXAMPLE 562 ##STR606## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol Melting Point:182.5°-183.5° C. Form: Free EXAMPLE 563 ##STR607## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol Melting Point:209°-211° C. Form: Free EXAMPLE 564 ##STR608## Crystalline form:Colorless prisms Recrystallization solvent: Dioxane Melting Point:210°-211° C. Form: Free EXAMPLE 565 ##STR609## Crystalline form:Colorless needles Recrystallization solvent: Ethyl acetate/n-hexaneMelting Point: 176°-178° C. Form: Free EXAMPLE 566 ##STR610##Crystalline form: Light yellow amorphous NMR analysis: 88) Form: FreeEXAMPLE 567 ##STR611## Crystalline form: White powder Recrystallizationsolvent: Dioxane/water Melting Point: 272°-273° C. Form: Free EXAMPLE568 ##STR612## Crystalline form: Colorless prisms Recrystallizationsolvent: Dioxane Melting Point: 253°-254° C. Form: Free EXAMPLE 569##STR613## Crystalline form: Colorless prisms Recrystallization solvent:Ethanol Melting Point: 248.5°-249.5° C. Form: Free EXAMPLE 570##STR614## Crystalline form: Colorless needles Recrystallizationsolvent: Ethanol Melting Point: 266.5°-267.5° C. Form: Free EXAMPLE 571##STR615## Crystalline form: Colorless needles Recrystallizationsolvent: Ethanol Melting Point: 252°-253° C. Form: Free EXAMPLE 572##STR616## Crystalline form: Light yellow powder NMR analysis: 89) Form:Free EXAMPLE 573 ##STR617## Crystalline form: Light brown powder NMRanalysis: 90) Form: Free EXAMPLE 574 ##STR618## Crystalline form: Whitepowder Recrystallization solvent: Diethyl ether Melting Point:198.5°-199.5° C. Form: Free EXAMPLE 575 ##STR619## Crystalline form:Colorless needles Recrystallization solvent: Ethanol Melting Point:297°-299° C. Form: Free EXAMPLE 576 ##STR620## Crystalline form:Colorless amorphous NMR analysis: 91) Form: Free EXAMPLE 577 ##STR621##Crystalline form: White powder Recrystallization solvent:Ethanol/petroleum ether Melting Point: 202°-203° C. Form: Free EXAMPLE578 ##STR622## Crystalline form: Colorless amorphous NMR analysis: 92)Form: Free EXAMPLE 579 ##STR623## Crystalline form: White powderRecrystallization solvent: Ethyl acetate/n-hexane Melting Point:232°-233° C. Form: Free EXAMPLE 580 ##STR624## Crystalline form:Colorless amorphous NMR analysis: 93) Form: Free EXAMPLE 581 ##STR625##Crystalline form: White powder Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 256.5°-257° C. Form: Free EXAMPLE 582##STR626## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 193°-194° C. Form: Free EXAMPLE583 ##STR627## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 227°-230° C. Form: Free EXAMPLE584 ##STR628## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 199.5°-202° C. Form: Free EXAMPLE585 ##STR629## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 219°-220° C. Form: Free EXAMPLE586 ##STR630## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 190°-191.5° C. Form: Free EXAMPLE587 ##STR631## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 184°-185° C. Form: Free EXAMPLE588 ##STR632## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 223°-224° C. Form: Free EXAMPLE589 ##STR633## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 178°-181° C. Form: Free EXAMPLE590 ##STR634## Crystalline form: Colorless needles Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 168°-168.5° C. Form: FreeEXAMPLE 591 ##STR635## Crystalline form: Colorless amorphous NMRanalysis: 94) Form: Free EXAMPLE 592 ##STR636## Crystalline form:Colorless amorphous NMR analysis: 95) Form: Free EXAMPLE 593 ##STR637##Crystalline form: White powder Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 196°-197° C. Form: Free EXAMPLE 594##STR638## Crystalline form: Colorless amorphous NMR analysis: 96) Form:Free EXAMPLE 595 ##STR639## Crystalline form: White powderRecrystallization solvent: Ethanol/water Melting Point: 188°-189° C.Form: Free EXAMPLE 596 ##STR640## Crystalline form: Colorless amorphousNMR analysis: 97) Form: Free EXAMPLE 597 ##STR641## Crystalline form:Colorless amorphous NMR analysis: 98) Form: Free EXAMPLE 598 ##STR642##Crystalline form: Colorless prisms Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 203°-204° C. Form: Free EXAMPLE 599##STR643## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 196°-197° C. Form: Free EXAMPLE600 ##STR644## Crystalline form: Colorless amorphous NMR analysis: 99)Form: Free EXAMPLE 601 ##STR645## Crystalline form: Colorless amorphousNMR analysis: 100) Form: Free EXAMPLE 602 ##STR646## Crystalline form:Colorless amorphous NMR analysis: 101) Form: Free EXAMPLE 603 ##STR647##Crystalline form: Colorless amorphous NMR analysis: 102) Form: FreeEXAMPLE 604 ##STR648## Crystalline form: Colorless amorphous NMRanalysis: 103) Form: Free EXAMPLE 605 ##STR649## Crystalline form:Colorless amorphous NMR analysis: 104) Form: Free EXAMPLE 606 ##STR650##Crystalline form: Colorless amorphous NMR analysis: 105) Form: FreeEXAMPLE 607 ##STR651## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol Melting Point: 169°-171° C. Form:Free EXAMPLE 608 ##STR652## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol/diethyl ether Melting Point:178°-181° C. Form: Free EXAMPLE 609 ##STR653## Crystalline form: Whitepowder Recrystallization solvent: Ethanol Melting Point: 187°-188° C.Form: Free EXAMPLE 610 ##STR654## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 181°-183° C. Form:Free EXAMPLE 611 ##STR655## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 124°-127° C. Form:Free EXAMPLE 612 ##STR656## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 179°-181° C. Form:Free EXAMPLE 613 ##STR657## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 148°-150° C. Form:Free EXAMPLE 614 ##STR658## Crystalline form: Colorless amorphous NMRanalysis: 106) Form: Free EXAMPLE 615 ##STR659## Crystalline form: Whitepowder Recrystallization solvent: Ethanol Melting Point: 219°-220° C.Form: Free EXAMPLE 616 ##STR660## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 226°-228° C. Form:Free EXAMPLE 617 ##STR661## Crystalline form: Colorless amorphous NMRanalysis: 107) Form: Free EXAMPLE 618 ##STR662## Crystalline form:Colorless amorphous NMR analysis: 108) Form: Free EXAMPLE 619 ##STR663##Crystalline form: Colorless amorphous NMR analysis: 109) Form: FreeEXAMPLE 620 ##STR664## Crystalline form: Colorless amorphous NMRanalysis: 110) Form: Free EXAMPLE 621 ##STR665## Crystalline form:Colorless amorphous NMR analysis: 111) Form: Free EXAMPLE 622 ##STR666##Crystalline form: Colorless amorphous NMR analysis: 112) Form: FreeEXAMPLE 623 ##STR667## Crystalline form: Colorless amorphous NMRanalysis: 113) Form: Free EXAMPLE 624 ##STR668## Crystalline form:Colorless amorphous NMR analysis: 114) Form: Free EXAMPLE 625 ##STR669##Crystalline form: Colorless amorphous NMR analysis: 115) Form: FreeEXAMPLE 626 ##STR670## Crystalline form: White powder Recrystallizationsolvent: Diethyl ether/dichloromethane Melting Point: 183°-184° C. Form:Free EXAMPLE 627 ##STR671## Crystalline form: White powderRecrystallization solvent: Diethyl ether/dichloromethane Melting Point:219°-220° C. Form: Free EXAMPLE 628 ##STR672## Crystalline form: Whitepowder Recrystallization solvent: Diethyl ether/dichloromethane MeltingPoint: 240°-241° C. Form: Free EXAMPLE 629 ##STR673## Crystalline form:White powder Recrystallization solvent: Diethyl ether/dichloromethaneMelting Point: 205°-206° C. Form: Free EXAMPLE 630 ##STR674##Crystalline form: White powder Recrystallization solvent: Diethylether/dichloromethane Melting Point: 238°-239° C. Form: Free EXAMPLE 631##STR675## Crystalline form: White powder Recrystallization solvent:Diethyl ether/dichloromethane Melting Point: 233°-234° C. Form: FreeEXAMPLE 632 ##STR676## Crystalline form: Colorless amorphous NMRanalysis: 116) Form: Free EXAMPLE 633 ##STR677## Crystalline form: Whitepowder Recrystallization solvent: Diethyl ether/dichloromethane MeltingPoint: 259.5°-260.5° C. Form: Free

80) ¹ H-NMR (CDCl₃) δ; 1.24-5.26 (18H, m), 6.39-7.59 (13H, m)

81) ¹ H-NMR (CDCl₃) δ; 1.70-2.10 (m, 2H), 2.15-2.60 (m, 12H), 3.56 (t,J=5.8 Hz, 1H), 3.65-3.95 (m, 4H) 4.05-4.25 (m, 1H), 6.64 (d, J=7.7 Hz,1H), 6.85-7.50 (m, 9H), 8.11 (brs, 1H), 8.42 (d, J=8.8 Hz, 1H)

82) ¹ H-NMR (CDCl₃) δ; 2.00-2.90 (m, 3H), 2.49 (s, 3H), 3.70-3.90 (m,1H), 4.00-4.20 (m, 1H), 4.80-5.00 (m, 1H), 6.89 (d, J=6.3 Hz, 1H),6.95-7.65 (m, 11H), 7.70 (brs, 1H)

83) ¹ H-NMR (CDCl₃) δ; 1.95-2.90 (m, 2H), 2.48 (s, 3H), 2.55 (s, 3H),3.77 (t, J=5.1 Hz, 1H), 3.92 (t, J=6.7 Hz, 2H), 6.72 (d, J=8.0 Hz, 1H),6.90-7.15 (m, 2H), 7.15-7.70 (m, 9H), 7.81 (brs, 1H)

84) ¹ H-NMR (CDCl₃) δ; 2.11 (s, 3H), 2.20-2.40 (m, 2H), 2.50 (s, 3H),3.80-4.10 (m, 1H), 4.12-4.25 (m, 1H), 6.03 (t, J=4.3 Hz, 1H), 6.80-7.65(m, 12H), 7.80 (brs, 1H)

85) ¹ H-NMR (CDCl₃) δ; 1.80-2.40 (m, 5H), 2.45 (s, 3H), 2.81 (s, 3H),3.55-3.82 (m, 1H), 4.15-4.40 (m, 1H), 5.90-6.10 (m, 1H), 6.80-7.80 (m,12H), 8.67 (brs, 1H)

86) ¹ H-NMR (CDCl₃) δ; 1.95-2.35 (2H, m), 2.75-3.0 (2H, m), 3.0-5.4 (2H,m), 6.55-7.95 (11H, m), 8.09 (1H, s)

87) ¹ H-NMR (DMSO-d₆) δ; 1.85-2.2 (2H, m), 2.7-2.95 (2H, m), 3.5-5.0(2H, m), 6.8-7.8 (12H, m), 10.60 (1H, s)

88) ¹ H-NMR (CDCl₃) δ; 0.8-1.1 (3H, m), 1.2-2.35 (6H, m), 2.35-5.25 (6H,m), 6.63 (1H, d, J=7.7 Hz), 6.8-7.6 (9H, m), 7.67 (1H, d, J=8.2 Hz),7.9-8.15 (1H, m)

89) ¹ H-NMR (CDCl₃) δ; 1.7-2.9 (7H, m), 4.5-6.5 (3H, m), 6.55-6.75 (1H,m), 6.85-7.6 (12H, m) 90) ¹ H-NMR (CDCl₃) δ; 1.65-3.1 (7H, m), 4.7-6.6(3H, m), 6.6-6.8 (1H, m), 6.85-7.65 (12H, m)

91) ¹ H-NMR (CDCl₃) δ; 1.8-2.4 (2H, m), 2.86 (2H, t, J=6 Hz), 3.1-5.15(2H, m), 6.85-7.5 (8H, m), 7.5-7.85 (3H, m), 8.19 (1H, s)

92) ¹ H-NMR (CDCl₃) δ; 1.46-2.28 (4H, m), 2.37 (3H, s), 2.58-2.90 (1H,m), 4.57-5.10 (2H, m), 6.59 (1H, d, J=7.6 Hz), 6.91-7.52 (11H, m), 7.62(1H, d, J=7.6 Hz), 8.10-8.40 (1H, m)

93) ¹ H-NMR (CDCl₃) δ; 1.45-1.91 (2H, m), 1.91-2.65 (2H, m), 2.65-2.901H, m), 4.63-5.22 (2H, m), 6.63 (1H, d, J=7.4 Hz), 34-8.03 (11H, m),10.16-10.44 (1H, m)

94) ¹ H-NMR (CDCl₃) δ; 1.08-1.47 (3H, m), 1.50-1.97 (2H, m), 1.97-2.48(2H, m), 2.65-3.02 (1H, m), 4.00-4.43 (4H, m), 4.52-5.15 (2H, m),6.50-6.79 (1H, m), 6.90-7.70 (10H, m), 8.26-8.60 (1H, m)

95) ¹ H-NMR (CDCl₃) δ; 1.56-2.67 (4H, m), 2.46 (3H, s), 2.67-3.03 (1H,m), 3.82-4.32 (2H, m), 4.45-5.15 (2H, m), 5.43-5.83 (1H, m), 6.20-6.45(1H, m), 6.50-6.86 (2H, m), 6.86-7.70 (10H, m), 7.76-8.10 (1H, m)

96) ¹ H-NMR (CDCl₃) δ; 1.52-1.90 (2H, m), 1.90-2.54 (2H, m), 2.67-3.05(1H, m), 3.74-4.32 (2H, m), 4.38-5.17 (2H, m), 5.52-5.98 (1H, brs),6.20-6.48 (1H, brs), 6.55-6.84 (1H, m), 6.89-7.55 (9H, m), 7.55-7.77(1H, m), 8.15-8.86 (1H, brs)

97) ¹ H-NMR (DMSO-d₆) δ; 1.26-2.49 (4H, m), 2.57-2.93 (1H, m), 4.07-4.43(2H, m), 4.44-4.98 (2H, m), 6.62-6.87 (1H, m), 6.92-7.80 (11H, m), 10.57(1H, s), 12.74 (1H, s)

98) ¹ H-NMR (CDCl₃) δ; 1.52-1.89 (2H, m), 1.89-2.56 (2H, m), 2.65-3.02(1H, m), 3.90-4.40 (2H, m), 4.40-5.07 (2H, m), 6.58-6.78 (1H, m),6.90-7.70 (10H, m), 8.57-8.81 (1H, brs)

99) ¹ H-NMR (CDCl₃) δ; 1.49-1.89 (2H, m), 1.89-2.60 (2H, m), 2.63-3.23(7H, m), 4.04-4.49 (2H, m), 4.52-5.21 (2H, m), 6.52-6.80 (1H, m),6.89-7.84 (10H, m), 8.08-8.52 (1H, m)

100) ¹ H-NMR (CDCl₃) δ; 1.41-1.86 (6H, m), 1.86-2.53 (4H, m), 2.25 (3H,s), 2.29 (3H, s), 2.43 (3H, s), 2.60-2.97 (1H, m), 3.36-3.77 (2H, m),4.40-5.10 (2H, m), 6.54-6.72 (1H, m), 6.88-7.67 (11H, m), 8.27-8.58 (1H,m)

101) ¹ H-NMR (CDCl₃) δ; 1.44-1.85 (6H, m), 1.85-2.61 (4H, m), 2.32 (3H,s), 2.35 (3H, s), 2.61-3.00 (1H, m), 3.33-3.76 (2H, m), 4.40-5.20 (2H,m), 6.57-6.75 (1H, m), 6.90-7.70 (11H, m), 8.50-8.93 (1H, m)

102) ¹ H-NMR (CDCl₃) δ; 1.49-2.04 (6H, m), 2.10-3.02 (5H, m), 2.47 (6H,s), 3.40-3.88 (2H, m), 4.30-5.17 (2H, m), 6.59-6.78 (1H, m), 6.93-7.76(10H, m), 8.75-9.40 (1H, m)

103) ¹ H-NMR (CDCl₃) δ; 1.47-2.47 (6H, m), 2.44 (3H, s), 2.62-3.03 (1H,m), 3.47-4.03 (4H, m), 4.48-5.17 (2H, m), 6.51-6.74 (1H, m), 6.87-7.62(11H, m), 7.62-7.77 (2H, 7.77-8.03 (3H, m)

104) ¹ H-NMR (CDCl₃) δ; 1.42-2.32 (6H, m), 2.44 (3H, s), 2.57-2.97 (1H,3.12-3.83 (4H, m), 4.39-5.13 (2H, m), 6.50-6.71 (1H, m), 6.90-7.73 (12H,m)

105) ¹ H-NMR (CDCl₃) δ; 1.50-2.63 (9H, m), 2.47 (3H, s), 2.66-3.07 (1H,m), 3.10-3.88 (4H, m), 4.40-5.17 (2H, m), 5.87-6.23 (1H, brs), 6.60-6.79(1H, m), 6.94-7.60 (11H, m), 7.67 (1H, s)

106) ¹ H-NMR (CDCl₃) δ; 1.20-2.53 (13H, 2.63-2.82, 3.00-3.13, 3.50-3.67,4.05-4.23 (total 3H, m), 6.55-8.00 (13H, m)

107) ¹ H-NMR (CDCl₃) δ; 1.41 (9H, s), 1.20-2.55 (10H, m), 3.42-4.20(5.8H, m), 5.00-5.20 (0.2H, m), 6.60-7.67 (10H, m), 7.99 (1H, brs), 8.26(1H, d, J=8.4 Hz)

108) ¹ H-NMR (CDCl₃) δ; 1.2-3.0 (10H, m), 3.0-5.2 (6H, m), 6.5-7.7 (8H,m), 8.22 (1H, d, J=8.4 Hz), 8.36 (1H, s)

109) ¹ H-NMR (CDCl₃) δ; 1.2-3.0 (10H, m), 3.0-5.2 (6H, m), 6.3-7.7 (10H,m)

110) ¹ H-NMR (CDCl₃) δ; 1.5-1.7 (1H, m), 2.2-2.7 (2H, m), 2.40 (6H, s),2.7-3.0 (3H, m), 5.1-5.3 (1H, m), 6.67 (1H, d, J=7.7 Hz), 6.9-7.5 (10H,m), 7.69 (1H, d, J=6 Hz), 8.06 (1H, s)

111) ¹ H-NMR (CDCl₃) δ; 1.4-1.7 (1H, m), 2.1-2.7 (2H, m), 2.40 (6H, s),2.44 (3H, s), 2.7-3.0 (3H, m), 5.1-5.3 (1H, m), 6.68 (1H, d, J=7.8 Hz),6.9-7.5 (11H, m), 7.66 (1H, s)

112) ¹ H-NMR (CDCl₃) δ; 1.5-1.8 (1H, m), 2.1-2.7 (2H, m), 2.38 (6H, s),2.7-3.0 (3H, m), 5.1-5.3 (1H, m), 6.66 (1H, d, J=7.7 Hz), 6.9-7.0 (9H,m), 7.57 (1H, d, J=8.3 Hz), 8.42 (1H, s)

113) ¹ H-NMR (CDCl₃) δ; 1.5-1.8 (1H, m), 2.1-2.7 (2H, m), 2.41 (6H, s),2.48 (3H, s), 2.7-3.0 (3H, m), 3.68 (3H, s), 5.2-5.4 (1H, m), 6.6-6.8(2H, m), 6.9-7.5 (8H, m), 8.09 (1H, s), 8.26 (1H, d, J=8.1 Hz)

114) ¹ H-NMR (CDCl₃) δ; 1.5-1.7 (1H, m), 2.1-2.3 (1H, 2.41 (6H, s),2.4-2.6 (1H, m), 2.8-3.0 (3H, m), 3.71 (3H, s), 5.2-5.4 (1H, m), 6.6-6.8(2H, m), 6.9-7.5 (7H, m), 7.7-7.8 (1H, m), 8.27 (1H, d, J=8.4 Hz), 8.57(1H, s)

115) ¹ H-NMR (CDCl₃) δ; 1.5-1.7 (1H, m), 2.1-2.7 (2H, m), 2.41 (6H, s),2.7-3.0 (3H, m), 3.71 (3H, s), 5.2-5.4 (1H, m), 6.6-7.6 (8H, m), 7.70(1H, d, J=8.3 Hz), 8.24 (1H, d, J=8.5 Hz), 8.59 (1H, s)

116) ¹ H-NMR (CDCl₃) δ; 1.8-2.3 (3H, m), 2.7-2.9 (2H, m), 3.5-3.7 (1H,m), 6.8-8.0 (10H, m), 8.7-9.1 (1H, br)

EXAMPLE 634

To a mixture of5-oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(4 g) and pyridine (50 ml) is added hydroxylamine hydrochloride (1.84 g)and the mixture is refluxed for 2.5 hours. The reaction solution isconcentrated and water is added to the resulting residue. Theprecipitated crystal is collected by filtration, and recrystallized fromdioxane/water to give5-hydroxyimino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2 g) as white powder, m.p. 272°-273° C.

EXAMPLE 635

5-Chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.8 g) is dissolved in dimethylformamide and thereto is added sodiumazide (0.18 g) at room temperature. The mixture is stirred at roomtemperature overnight, and further reacted with heating at 50° C. for 5hours. Water is added to the reaction mixture and the precipitatedcrystal is collected by filtration to give5-azido-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.68 g) as light brown powder.

¹ H-NMR (CDCl₃) δ; 1.65-3.1 (8H, m), 4.7-6.6 (3H, m), 6.6-6.8 (1H, m),6.85-7.65 (12H, m)

EXAMPLE 636

5-Azido-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.63 g) is dissolved in ethanol and thereto is added 10% Pd-C (0.1 g).The mixture is subjected to catalytic hydrogenation at room temperatureunder 1 atm. of hydrogen. Pd-C is removed by filtration and the filtrateis evaporated. The resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=50:1), andrecrystallized from diethyl ether to give5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.34 g) as white powder, m.p. 198.5°-199.5° C.

EXAMPLE 637

To5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.58 g) are added acetic anhydride (8.0 ml) and pyridine (2.0 ml). Themixture is stirred at room temperature for 1 hour. Water is added to thereaction mixture and the precipitated crystal is collected byfiltration, and recrystallized from ethyl acetate/n-hexane to give5-acetyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.56 g) as white powder, m.p. 193°-194° C.

EXAMPLE 638

5-Ethoxycarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.00 g) is dissolved in methanol (35 ml) and thereto are added aqueousammonia (20 ml) and ammonium chloride (0.50 g). The mixture is heated at100° C. for 3.5 hours in a sealed tube. After cooling, the reactionsolution is concentrated under reduced pressure and acidified withhydrochloric acid, and extracted with dichloromethane. The extract isdried over magnesium sulfate and the solvent is distilled off. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=15:1) to give5-carbamoylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.68 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.56-2.67 (4H, m), 2.46 (3H, s), 2.67-3.03 (1H, m),3.82-4.32 (2H, m), 4.45-5.15 (2H, m), 5.43-5.83 (1H, m), 6.20-6.45 (1H,m), 6.50-6.86 (2H, m), 6.86-7.70 (10H, m), 7.76-8.10 (1H, m)

Using the suitable starting materials, the compounds of the aboveExamples 593 and 594 are obtained in the same manner as in Example 638.

EXAMPLE 639

5-Ethoxycarbonylmethoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.94 g) is dissolved in ethanol (100 ml) and thereto is added 5Naqueous sodium hydroxide solution (0.50 ml). The mixture is stirred atroom temperature for 2 hours. The reaction solution is concentratedunder reduced pressure and to the resulting residue is added dilutedhydrochloric acid and then extracted with dichloromethane. The extractis dried over magnesium sulfate and the solvent is distilled off. Theresulting residue is washed with n-hexane and collected by filtration togive5-carboxymethoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.79 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.52-1.89 (2H, m), 1.89-2.56 (2H, m), 2.65-3.02 (1H,m), 3.90-4.40 (2H, m), 4.40-5.07 (2H, m), 6.58-6.78 (1H, m), 6.90-7.70(10H, m), 8.57-8.81 (1H, brs)

Using the suitable starting materials, the compounds of the aboveExamples 595 and 596 are obtained in the same manner as in Example 639.

EXAMPLE 640

5-Carboxymethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g) is dissolved in dimethylformamide (20 ml) and thereto are addeddimethylamine hydrochloride (0.20 g) and diethyl chlorophosphate (0.33g). To the mixture is added triethylamine (1.0 ml) under ice-cooling,and the mixture is stirred under ice-cooling for 30 minutes, and at roomtemperature for more 2 hours. Water is added to the reaction solutionand the precipitated crystal is collected by filtration andrecrystallized from ethyl acetate/n-hexane to give5-dimethylaminocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) as colorless prisms, m.p. 203°-204° C.

Using the suitable starting materials, the compounds of the aboveExamples 599 and 600 are obtained in the same manner as in Example 640.

EXAMPLE 641

5-[3-(Phthalimid-1-yl)propoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.26 g) is dissolved in ethanol (100 ml) and thereto is added hydrazinehydrate (1.0 ml). The mixture is refluxed with stirring for 1 hour. Thereaction solution is evaporated under reduced pressure and to theresulting residue is added dichloromethane. The insoluble materials areremoved by filtration. The filtrate is purified by silica gel columnchromatography (eluent; dichloromethane:methanol:aqueousammonia=70:10:1) to give5-(3-aminopropoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.42-2.32 (6H, m), 2.44 (3H, s), 2.57-2.97 (1H, m),3.12-3.83 (4H, m), 4.39-5.13 (2H, m), 6.50-6.71 (1H, m), 6.90-7.73 (12H,m)

EXAMPLE 642

A solution of5-dimethylamino-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) in dichloromethane (30 ml) is added dropwise to a solution of1M boron tribromide in dichloromethane (5.46 ml) at -45° C. Aftercompletion of the dropping, the mixture is stirred for 1 day while thetemperature of the reaction mixture is gradually raised to roomtemperature. To the reaction solution is added water and the mixture isneutralized with sodium hydrogen carbonate, and extracted withdichloromethane. The extract is washed with saturated saline solutionand dried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; chloroform:methanol=500:1), and recrystallized frommethanol/diethyl ether to give5-dimethylamino-1-[3-hydroxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.33 g) as white powder, m.p. 201.5°-202.5° C.

Using the suitable starting materials, the compounds of the aboveExamples 10, 32, 343, 356, 535, 555 and 556 are obtained in the samemanner as in Example 642.

EXAMPLE 643

To a solution of4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzazepine (0.5g) in dichloromethane (10 ml) is added m-chloroperbenzoic acid (0.58 g)under ice-cooling, and the mixture is stirred at room temperature for 6hours. The above reaction solution is poured into an aqueous solution ofsodium carbonate (0.6 g) in water (10 ml) and the mixture is extractedwith dichloromethane. The extract is washed with water, and dried overmagnesium sulfate. The solvent is distilled off under reduced pressureand the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=100:1), andrecrystallized from diethyl ether/dichloromethane to give4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazine-1,1-dioxide(0.49 g) as white powder, m.p. 219°-220° C.

Using the suitable starting materials, the compound of the above Example630 is obtained in the same manner as in Example 643.

EXAMPLE 644

To a suspension of4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazine(0.5 g) in methanol (15 ml) is added an aqueous solution of sodiummetaperiodate (0.28 g) in water (2.5 ml) and the mixture is stirred atroom temperature for 72 hours. Water is added to the reaction solutionand extracted with dichloromethane. The extract is dried over magnesiumsulfate and the solvent is distilled off under reduced pressure. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=100:1), and recrystallized fromdichloromethane/diethyl ether to give4-[4-(2-methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazin-1-oxide(0.34 g) as white powder, m.p. 240°-241° C.

Using the suitable starting materials, the compound of the above Example631 is obtained in the same manner as in Example 644.

EXAMPLE 645

5-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3.57 g) is dissolved in dichloromethane (30 ml) and pyridine (1.1 ml),and thereto is added dropwise methanesulfonyl chloride (0.9 ml) in smallportions at 0° C. Then, the mixture is stirred at room temperature for 3days. The solvent is distilled off and the resulting residue is pouredinto ice-water. The precipitated crystal is collected by filtration,washed with water, and dried to give5-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3.10 g) as light yellow powder.

¹ H-NMR (CDCl₃) δ; 1.7-2.9 (8H, m), 4.5-6.5 (3H, m), 6.55-6.75 (1H, m),6.85-7.6 (12H, m)

EXAMPLE 646

5-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.69 g) is dissolved in dimethylformamide (30 ml) and thereto are added60% sodium hydride dispersion in mineral oil (0.44 g) and ethylbromoacetate (1.00 ml) under ice-cooling, and the mixture is stirred atroom temperature for 4 hours. The reaction solution is poured into anaqueous ammonium chloride solution under ice-cooling, and extracted withethyl acetate. The extract is dried over magnesium sulfate and thesolvent is distilled off. The resulting residue is purified by silicagel column chromatography (eluent; ethyl acetate:n-hexane=1:2), andrecrystallized from ethyl acetate/n-hexane to give5-ethoxycarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl-2,3,4,5-tetrahydro-1H-benzazepine(2.10 g) as white powder, m.p. 178°-181° C.

Using the suitable starting materials, the compounds of the aboveExamples 585-588 and 590-606 are obtained in the same manner as inExample 646.

EXAMPLE 647

Using the suitable starting materials, the compounds of the aboveExamples 546 and 578-581 are obtained in the same manner as in Example384.

EXAMPLE 648

Using the suitable starting materials, the compounds of the aboveExamples 537-545, 547, 549-556, 561-564, 566, 568-571, 577, 601-603 and607-625 are obtained in the same manner as in Example 388.

EXAMPLE 649

Using the suitable starting materials, the compounds of the aboveExamples 549, 568-571, 575 and 606 are obtained in the same manner as inExample 389.

EXAMPLE 650

Using the suitable starting materials, the compounds of the aboveExamples 537-545, 547, 549-556, 561-566, 568-571, 575, 577, 607, 608 and613-625 are obtained in the same manner as in Example 390.

EXAMPLE 651

Using the suitable starting materials, the compounds of the aboveExamples 601-603, 605 and 606 are obtained in the same manner as inExample 397.

EXAMPLE 652

Using the suitable starting materials, the compound of the above Example604 is obtained in the same manner as in Example 398.

EXAMPLE 653

Using the suitable starting materials, the following compound isobtained in the same manner as in Examples 1, 382, 388 and 390.

5-Methylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 184.5°-185.5° C. (recrystallized from ethanol)

Using the suitable starting materials, the compounds of the followingTable 4 are obtained in the same manner as in Examples 1 and 382.##STR678##

EXAMPLE 654 ##STR679## Crystalline form: White powder Recrystallizationsolvent: Methanol/n-hexane Melting Point: 193.5°-196° C. Form: FreeEXAMPLE 655 ##STR680## Crystalline form: White powder Recrystallizationsolvent: Methanol/n-hexane Melting Point: 195°-198° C. Form: FreeEXAMPLE 656 ##STR681## Crystalline form: White powder Recrystallizationsolvent: Methanol Melting Point: 230.5°-231.5° C. Form: Free EXAMPLE 657##STR682## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 223°-224.5° C. Form: Free EXAMPLE658 ##STR683## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 173°-174° C. Form: Free EXAMPLE659 ##STR684## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 174°-175° C. Form: Free EXAMPLE660 ##STR685## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 198°-200° C. Form: Free EXAMPLE661 ##STR686## Crystalline form: White powder Recrystallization solvent:Methanol/n-hexane Melting Point: 149°-150.5° C. Form: Free EXAMPLE 662##STR687## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 183°-185° C. Form: Free EXAMPLE663 ##STR688## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 203°-207° C. Form: Free EXAMPLE664 ##STR689## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 221°-222° C. Form: Free EXAMPLE665 ##STR690## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 189°-191° C. Form: Free EXAMPLE666 ##STR691## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 215.5°-217° C. Form: Free EXAMPLE667 ##STR692## Crystalline form: White powder Recrystallization solvent:Methanol/n-hexane Melting Point: 192°-194° C. Form: Free EXAMPLE 668##STR693## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 195°-196° C. Form: Free EXAMPLE669 ##STR694## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 202°-204.5° C. Form: Free EXAMPLE670 ##STR695## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 183°-187° C. Form: Free EXAMPLE671 ##STR696## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 120°-122° C. Form: Free EXAMPLE672 ##STR697## Crystalline form: White powder Recrystallization solvent:Chloroform/diethyl ether Melting Point: 208°-210° C. Form: Free EXAMPLE673 ##STR698## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 182°-183° C. Form: Free EXAMPLE674 ##STR699## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 257°-259° C. Form: Free EXAMPLE675 ##STR700## Crystalline form: White powder Recrystallization solvent:Dichloromethane/diethyl ether Melting Point: 134°-135° C. Form: FreeEXAMPLE 676 ##STR701## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 167°-169° C. Form: FreeEXAMPLE 677 ##STR702## Crystalline form: Light brown prismsRecrystallization solvent: Ethyl acetate/n-hexane Melting Point:170°-172° C. Form: Free EXAMPLE 678 ##STR703## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:181.5°-182.5° C. Form: Free EXAMPLE 679 ##STR704## Crystalline form:White powder Recrystallization solvent: Ethyl acetate/n-hexane MeltingPoint: 176.5°-177° C. Form: Free EXAMPLE 680 ##STR705## Crystallineform: Yellow amorphous NMR analysis: 117) Form: Free EXAMPLE 681##STR706## Crystalline form: Yellow amorphous NMR analysis: 118) Form:Free EXAMPLE 682 ##STR707## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 236°-239° C. Form:Free EXAMPLE 683 ##STR708## Crystalline form: White powderRecrystallization solvent: Ethyl acetate/n-hexane Melting Point:153°-154° C. Form: Free EXAMPLE 684 ##STR709## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate Melting Point: 128°-130°C. Form: Free EXAMPLE 685 ##STR710## Crystalline form: White powderRecrystallization solvent: Ethanol/diethyl ether Melting Point:231°-234° C. Form: Free EXAMPLE 686 ##STR711## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate Melting Point: 246°-248°C. Form: Free EXAMPLE 687 ##STR712## Crystalline form: White powderRecrystallization solvent: Ethanol/water Melting Point: 248°-248.5° C.Form: Free EXAMPLE 688 ##STR713## Crystalline form: White powderRecrystallization solvent: Dichloromethane/diethyl ether Melting Point:204°-205° C. Form: Free EXAMPLE 689 ##STR714## Crystalline form: Whitepowder Recrystallization solvent: Dichloromethane/diethyl ether MeltingPoint: >300° C. NMR analysis: 119) Form: Free EXAMPLE 690 ##STR715##Crystalline form: White powder Recrystallization solvent:Dichloromethane/diethyl ether Melting Point: 292°-294° C. Form: FreeEXAMPLE 691 ##STR716## Crystalline form: Colorless amorphous NMRanalysis: 120) Form: Free EXAMPLE 692 ##STR717## Crystalline form:Colorless amorphous NMR analysis: 121) Form: Free EXAMPLE 693 ##STR718##Crystalline form: Colorless amorphous NMR analysis: 122) Form: FreeEXAMPLE 694 ##STR719## Crystalline form: Colorless amorphous NMRanalysis: 123) Form: Free EXAMPLE 695 ##STR720## Crystalline form: Whitepowder Recrystallization solvent: Ethanol Melting Point: 198.5°-199° C.Form: Free EXAMPLE 696 ##STR721## Crystalline form: White powderRecrystallization solvent: Diethyl ether/dichloromethane Melting Point:168°-170° C. Form: Free EXAMPLE 697 ##STR722## Crystalline form: Whitepowder Recrystallization solvent: Diethyl ether/dichloromethane MeltingPoint: 175°-176° C. Form: Free EXAMPLE 698 ##STR723## Crystalline form:White powder Recrystallization solvent: Diethyl ether/dichloromethaneMelting Point: 177°-178° C. Form: Free EXAMPLE 699 ##STR724##Crystalline form: White powder Recrystallization solvent: Diethylether/dichloromethane Melting Point: 222°-223.5° C. Form: Free EXAMPLE700 ##STR725## Crystalline form: White powder Recrystallization solvent:Diethyl ether/dichloromethane Melting Point: 243°-244° C. Form: FreeEXAMPLE 701 ##STR726## Crystalline form: White powder Recrystallizationsolvent: Diethyl ether/dichloromethane Melting Point: 180°-181° C. Form:Free EXAMPLE 702 ##STR727## Crystalline form: Colorless amorphous NMRanalysis: 124) Form: Free EXAMPLE 703 ##STR728## Crystalline form: Whitepowder Recrystallization solvent: Diethyl ether/dichloromethane MeltingPoint: 231°-233° C. Form: Free EXAMPLE 704 ##STR729## Crystalline form:White powder Recrystallization solvent: Diethyl ether/dichloromethaneMelting Point: 196°-198° C. Form: Free EXAMPLE 705 ##STR730##Crystalline form: Colorless amorphous NMR analysis: 125) Form: FreeEXAMPLE 706 ##STR731## Crystalline form: Yellow amorphous NMR analysis:126) Form: Free EXAMPLE 707 ##STR732## Crystalline form: Yellow powderRecrystallization solvent: Diethyl ether/dichloromethane Melting Point:146°-147° C. Form: Free EXAMPLE 708 ##STR733## Crystalline form:Colorless amorphous NMR analysis: 127) Form: Free EXAMPLE 709 ##STR734##Crystalline form: White powder Recrystallization solvent: Diethylether/dichloromethane Melting Point: 220°-221° C. Form: Free EXAMPLE 710##STR735## Crystalline form: White powder Recrystallization solvent:Diethyl ether/dichloromethane Melting Point: 170°-172° C. Form: FreeEXAMPLE 711 ##STR736## Crystalline form: Colorless amorphous NMRanalysis: 128 Form: Free EXAMPLE 712 ##STR737## Crystalline form: Whitepowder Recrystallization solvent: Ethanol Melting Point: 224°-225° C.Form: Free EXAMPLE 713 ##STR738## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 193°-196° C. Form:Free EXAMPLE 714 ##STR739## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 212°-214° C. Form:Free EXAMPLE 715 ##STR740## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 211°-213° C. Form:Free EXAMPLE 716 ##STR741## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 213°-215° C. Form:Free EXAMPLE 717 ##STR742## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 199°-201° C. Form:Free EXAMPLE 718 ##STR743## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 238°-240° C. Form:Free EXAMPLE 719 ##STR744## Crystalline form: White powderRecrystallization solvent: Ethanol Melting Point: 188°-189° C. Form:Free EXAMPLE 720 ##STR745## Crystalline form: Colorless prismsRecrystallization solvent: Dioxane/water Melting Point: 135.5°-137° C.Form: Free EXAMPLE 721 ##STR746## Crystalline form: White powderRecrystallization solvent: Isopropyl alcohol/petroleum ether MeltingPoint: 192°-193° C. Form: Free EXAMPLE 722 ##STR747## Crystalline form:Colorless needles Recrystallization solvent: Ethyl acetate MeltingPoint: 239°-240° C. Form: Free EXAMPLE 723 ##STR748## Crystalline form:Colorless amorphous NMR analysis: 129) Form: Free EXAMPLE 724 ##STR749##Crystalline form: Colorless amorphous NMR analysis: 130) Form: FreeEXAMPLE 725 ##STR750## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol/petroleum ether Melting Point:193°-194° C. Form: Free EXAMPLE 726 ##STR751## Crystalline form: Lightyellow prisms Recrystallization solvent: Ethanol Melting Point:245.5°-247° C. Form: Free EXAMPLE 727 ##STR752## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol/petroleum etherMelting Point: 142°-144° C. Form: Free EXAMPLE 728 ##STR753##Crystalline form: Light yellow prisms Recrystallization solvent: EthanolMelting Point: 214°-217° C. Form: Free EXAMPLE 729 ##STR754##Crystalline form: Colorless needles Recrystallization solvent: EthanolMelting Point: 205°-207° C. Form: Free EXAMPLE 730 ##STR755##Crystalline form: Colorless needles Recrystallization solvent:Ethanol/diethyl ether Melting Point: 201°-203° C. Form: Free EXAMPLE 731##STR756## Crystalline form: Colorless needles Recrystallizationsolvent: Ethanol/diethyl ether Melting Point: 180°-182° C. Form: FreeEXAMPLE 732 ##STR757## Crystalline form: Light yellow scalesRecrystallization solvent: Ethanol/diethyl ether Melting Point:178°-180° C. Form: Free EXAMPLE 733 ##STR758## Crystalline form:Colorless needles Recrystallization solvent: Methanol/diethyl etherMelting Point: 208°-213° C. Form: Free EXAMPLE 734 ##STR759##Crystalline form: White powder Recrystallization solvent:Ethanol/diethyl ether Melting Point: 175°-177° C. Form: Free EXAMPLE 735##STR760## Crystalline form: White powder NMR analysis: 131) Form: FreeEXAMPLE 736 ##STR761## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 277°-279° C. Form: FreeEXAMPLE 737 ##STR762## Crystalline form: Colorless amorphous NMRanalysis: 132) Form: Free EXAMPLE 738 ##STR763## Crystalline form:Colorless amorphous NMR analysis: 133) Form: Free EXAMPLE 739 ##STR764##Crystalline form: Colorless amorphous NMR analysis: 134) Form: FreeEXAMPLE 740 ##STR765## Crystalline form: Colorless amorphous NMRanalysis: 135) Form: Free EXAMPLE 741 ##STR766## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:213°-214° C. Form: Free EXAMPLE 742 ##STR767## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:216°-217° C. Form: Free EXAMPLE 743 ##STR768## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:165°-167° C. Form: Free EXAMPLE 744 ##STR769## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:202°-206° C. Form: Free EXAMPLE 745 ##STR770## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:220°-221.5° C. Form: Free EXAMPLE 746 ##STR771## Crystalline form:Colorless needles Recrystallization solvent: Ethyl acetate/n-hexaneMelting Point: 186°-186.5° C. Form: Free EXAMPLE 747 ##STR772##Crystalline form: Colorless amorphous NMR analysis: 136) Form: FreeEXAMPLE 748 ##STR773## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 136°-140° C. Form: FreeEXAMPLE 749 ##STR774## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 151°-153° C. Form: FreeEXAMPLE 750 ##STR775## Crystalline form: Colorless needlesRecrystallization solvent: Ethyl acetate/n-hexane Melting Point:155°-156° C. Form: Free EXAMPLE 751 ##STR776## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:189°-190° C. Form: Free EXAMPLE 752 ##STR777## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:188°-190° C. Form: Free EXAMPLE 753 ##STR778## Crystalline form:Colorless needles Recrystallization solvent: Ethanol Melting Point:233°-235° C. Form: Free EXAMPLE 754 ##STR779## Crystalline form:Colorless amorphous NMR analysis: 137) Form: Free EXAMPLE 755 ##STR780##Crystalline form: White powder Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 176°-179° C. Form: Free EXAMPLE 756##STR781## Crystalline form: Colorless needles Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 183°-185° C. Form: Free

117) ¹ H-NMR (CDCl₃) δ; 1.3-2.3 (4H, m), 3.1-3.4 (3H, m), 3.8-4.6 (2H,m), 5.0-5.3 (2H, m), 5.8-6.1 (1H, m), 6.8-8.5 (11H, m)

118) ¹ H-NMR (CDCl₃) δ; 1.6-2.2 (4H, m), 2.46, 2.53 (3H, each s),3.1-3.5 (3H, m), 3.8-4.6 (2H, m), 5.0-5.3 (2H, m), 5.8-6.1 (1H, m),6.8-8.0 (11H, m) 119) ¹ H-NMR (DMSO-d₆) δ; 2.33 (3H, s), 3.36 (2H, m),3.89 (1H, m), 4.41 (1H, m), 5.07 (1H, m), 5.40 (1H, d, J=14.8 Hz), 6.85(1H, d, J=7.2 Hz), 7.15-7.65 (11H, m), 10.35 (1H, s)

120) ¹ H-NMR (CDCl₃) δ; 1.25-5.05 (22H, m), 6.65-7.65 (11H, m),7.75-8.25 (1H, m)

121) ¹ H-NMR (CDCl₃) δ; 1.15-5.05 (19H, m), 6.75-7.85 (11H, m),7.85-8.25 (1H, m)

122) ¹ H-NMR (CDCl₃) δ; 1.25-2.85 (8H, m), 2.95-4.95 (2H, m), 6.75-7.85(10H, m), 9.25-9.75 (1H, m)

123) ¹ H-NMR (CDCl₃) δ; 0.20-0.70 (4H, m), 0.95-2.35 (6H, m), 2.65-5.00(2H, m), 6.75-7.90 (10H, m), 8.65-9.25 (1H, m)

124) ¹ H-NMR (CDCl₃) δ; 1.20-3.15 (11H, m), 3.45-3.70 (1H, m), 4.05-5.20(1H, m), 6.60-7.65 (10H, m), 8.15-8.45 (2H, m)

125) ¹ H-NMR (CDCl₃) δ; 1.19 (3H, t, J=7 Hz), 1.25-3.25 (8H, m), 3.46(2H, q, J=7 Hz), 3.40-4.10 (3H, m), 4.45-5.10 (1H, m), 6.65-7.75 (12H,m), 8.30-8.60 (1H, m)

126) ¹ H-NMR (CDCl₃) δ; 1.10-1.30 (3H, m), 1.50-2.35 (4H, m), 2.65-3.05(2H, m), 3.35-3.60 (2H, m), 3.80-4.05 (2H, m), 4.65-5.15 (2H, m),6.55-7.85 (12H, m), 8.35-8.65 (1H, m)

127) ¹ H-NMR (CDCl₃) δ; 1.20 (3H, t, J=7 Hz), 1.10-3.15 (11H, m),3.45-3.65 (3H, m), 3.88 (2H, s), 3.95-5.15 (1H, m), 6.55-7.65 (13H, m),8.37 (1H, s)

128) ¹ H-NMR (CDCl₃) δ; 2.45 (3H, s), 3.40 (3H, s), 4.01 (2H, m), 4.38(2H, m), 7.20-7.77 (13H, m)

129) ¹ H-NMR (CDCl₃) δ; 1.35-4.55 (22H, m), 6.3-7.8 (13H, m)

130) ¹ H-NMR (CDCl₃) δ; 1.10 (6H, t, J=7 Hz), 1.35-5.1 (23H, m),6.55-7.8 (13H, m)

131) ¹ H-NMR (CDCl₃) δ; 1.94-3.21 (3H, m), 3.30-4.82 (3H, m), 6.57 (1H,d, J=7.5 Hz), 6.86-8.10 (11H, m), 8.72 (1H, brs)

132) ¹ H-NMR (DMSO-d₆) δ; 1.57-1.85 (2H, m), 1.85-2.28 (2H, m), 2.33(3H, s), 2.64-2.86 (1H, m), 4.53-5.07 (1H, m), 5.79-5.94 (1H, m),6.47-7.68 (2H, br), 6.64-6.77 (1H, m), 6.96-7.62 (12H, m)

133) ¹ H-NMR (CDCl₃) δ; 1.61-1.97 (2H, m), 2.00-2.54 (2H, m), 2.47 (3H,s), 2.60-3.23 (7H, m), 4.76-5.22 (1H, m), 5.94-6.19 (1H, m), 6.61-6.74(1H, m), 6.91-7.62 (12H, m)

134) ¹ H-NMR (CDCl₃) δ; 1.68-1.97 (2H, m), 2.03-2.53 (2H, m), 2.61-3.24(7H, m), 4.76-5.22 (1H, m), 5.97-6.17 (1H, m), 6.59-6.74 (1H, m),6.92-7.13 (1H, m), 7.13-7.58 (9H, m), 7.66-7.85 (1H, m), 7.85-8.00 (1H,m)

135) ¹ H-NMR (CDCl₃) δ; 1.57-1.93 (2H, m), 1.93-2.54 (2H, m), 2.54-2.72(1H, m), 2.79-3.09 (3H, m), 3.90-4.32 (2H, m), 4.49-5.18 (2H, m),6.31-6.93 (2H, m), 6.96-7.63 (10H, m), 7.63-7.89 (1H, m), 7.89-8.16 (1H,m)

136) ¹ H-NMR (CDCl₃) δ; 1.44-1.95 (2H, m), 1.95-2.28 (2H, m), 2.40-2.67(3H, m), 2.73-3.38 (3H, m), 3.40-3.97 (1H, m), 4.50-5.20 (1H, m),6.67-8.11 (11H, m)

137) ¹ H-NMR (CDCl₃) δ; 1.50-2.10 (3H, m), 2.10-2.28 (1H, m), 2.36 (3H,s), 2.48 (3H, s), 2.68-2.97 (1H, m), 3.26-3.47 (1H, m), 4.16 (1H, d,J=13.8 Hz), 4.25 (1H, d, J=13.8 Hz), 5.95 (1H, brs), 6.60-6.76 (1H, m),6.97-7.52 (8H, m), 7.52-7.73 (2H, m), 7.73-7.97 (2H, m)

EXAMPLE 757

A mixture of5-dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(10 g), methyl iodide (1.7 ml) and chloroform (10 ml) is heated withstirring at 100° C. for 3 hours in an autoclave. After completion of thereaction, the solvent is distilled off under reduced pressure and theresulting residue is dissolved in methanol. The mixture is treated withIRA-400 (trade mark; Organo Co., Ltd., OH⁻ type). Methanol is distilledoff and the resulting residue is suspended in t-butyl alcohol (90 ml),and thereto is added potassium t-butoxide (2.3 g). The mixture isrefluxed for 5 hours. The solvent is distilled off under reducedpressure, and the resulting residue is dissolved in dichloromethane. Themixture is washed successively with water and saturated saline solutionand dried over magnesium sulfate. The solvent is distilled off and tothe resulting residue is added dichloromethane/diethyl ether. Theprecipitated crude crystal is recrystallized from ethanol to give1-[4-(2-chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine (5.15 g)as colorless needles, m.p. 205°-207° C.

EXAMPLE 758

1-[4-(2-Chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine (4.7 g)is dissolved in dichloromethane (50 ml) and thereto is added 80%m-chloroperbenzoic acid (3 g). The mixture is stirred at roomtemperature overnight. The dichloromethane layer is washed successivelywith saturated aqueous sodium hydrogen carbonate solution and saturatedsaline solution, and the solvent is distilled off under reducedpressure. The resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=50:1) to give4,5-epoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(4.26 g) as white powder.

¹ H-NMR (CDCl₃) δ; 1.94-3.21 (3H, m), 3.30-4.82 (3H, m), 6.57 (1H, d,J=7.5 Hz), 6.86-8.10 (11H, m), 8.72 (1H, brs)

EXAMPLE 759

A mixture of4,5-epoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.5 g), dimethylamine hydrochloride (2.6 g), triethylamine (4.5 g) andmethanol (15 ml) is refluxed for 19 hours. After completion of thereaction, the solvent is distilled off and the resulting residue isdissolved in dichloromethane. The mixture is washed successively withwater and saturated saline solution. The solvent is distilled off andthe resulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=50:1), and recrystallized fromethanol/diethyl ether to givetrans-5-dimethylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.38 g) as colorless needles, m.p. 180°-182° C.

Using the suitable starting materials, the compounds of the aboveExample 733 and 734 are obtained in the same manner as in Example 759.

EXAMPLE 760

Methyltriphenylphosphonium bromide (4.30 g) is suspended intetrahydrofuran (100 ml) and thereto is added potassium t-butoxide (1.58g) under ice-cooling. The mixture is stirred at -5° C. for 1 hour andthereto is added5-oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.60 g) and the mixture is stirred at room temperature for 1 hour. Thereaction solution is poured into ice-water (200 ml) and extracted withethyl acetate. The extract is washed with saturated saline solution anddried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; ethyl acetate:n-hexane=1:2), and recrystallized from ethylacetate/n-hexane to give5-methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.34 g) as white powder, m.p. 216°-217° C.

Using the suitable starting materials, the compound of the above Example743 is obtained in the same manner as in Example 760.

EXAMPLE 761

5-Methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.84 g) is suspended in tetrahydrofuran (50 ml) and thereto is added 1Msolution of boran-tetrahydrofuran complex in tetrahydrofuran (43 ml).The mixture is stirred at room temperature for 6 hours. After completionof the reaction, the reaction solution is cooled with ice, and theretois added water (70 ml). After termination of the evolution of hydrogengas, to the reaction solution are added 25% aqueous sodium hydroxidesolution (7.0 ml), and subsequently 31% aqueous hydrogen peroxidesolution (4.7 ml), and the mixture is heated with stirring at 50° C. for1 hour. After cooling, to the reaction solution is added saturatedsaline solution and the tetrahydrofuran layer is collected, washed withsaturated saline solution and dried over magnesium sulfate. The solventis distilled off and the resulting residue is recrystallized from ethylacetate/n-hexane to give5-hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.96 g) as white powder, m.p. 202°-206° C.

Using the suitable starting materials, the compound of the above Example745 is obtained in the same manner as in Example 761.

EXAMPLE 762

5-Methylidene-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.81 g) is dissolved in dichloromethane (30 ml) and thereto is addedm-chloroperbenzoic acid (0.57 g). The mixture is stirred at roomtemperature for 15 hours. After completion of the reaction, the reactionsolution is washed successively with aqueous sodium hydrogensulfitesolution, aqueous sodium hydrogen carbonate solution and saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified with silica gelcolumn chromatography (eluent; ethyl acetate:n-hexane=2:3) to give5,5-epoxy-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.44-1.95 (2H, m), 1.95-2.28 (2H, m), 2.40-2.67 (3H,m), 2.73-3.38 (3H, m), 3.40-3.97 (1H, m), 4.50-5.20 (1H, m), 6.67-8.11(11H, m)

Using the suitable starting materials, the compound of the above Example746 is obtained in the same manner as in Example 762.

EXAMPLE 763

To5-methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.60 g) are added successively t-butyl alcohol (6.0 ml), water (1.2ml), pyridine (0.3 ml), osmium tetroxide (1.2 mg) and trimethylamineN-oxide dihydrate (0.22 g), and the mixture is refluxed with stirringfor 2.5 hours. After cooling, to the reaction solution is added 20%aqueous sodium hydrogensulfite solution (10 ml), and the mixture isstirred at room temperature for 1.5 hour. The reaction solution isextracted with a mixture of ethyl acetate/tetrahydrofuran (1:1). Theextract is washed successively with diluted hydrochloric acid andsaturated saline solution, and dried over magnesium sulfate. The solventis distilled off and the resulting residue is recrystallized from ethylacetate/n-hexane to give5-hydroxymethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g) as white powder, m.p. 136°-140° C.

Using the suitable starting materials, the compound of the above Example749 is obtained in the same manner as in Example 763.

EXAMPLE 764

To5-hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.40 g) are added acetic anhydride (4.0 ml) and pyridine (0.5 ml), andthe mixture is stirred at room temperature for 5 hours. After completionof the reaction, the reaction solution is poured into ice-water andextracted with ethyl acetate. The extract is washed successively withdiluted hydrochloric acid and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is recrystallized from ethyl acetate/n-hexane to give5-acetyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.43 g) as colorless needles, m.p. 155°-156° C.

EXAMPLE 765

5-Hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.70 g) is dissolved in a mixture (30 ml) ofdichloromethane/acetonitrile (1:1) and thereto are added methanesulfonylchloride (0.8 ml) and pyridine (1.0 ml), and the mixture is refluxedwith stirring for 2 hours. After cooling, the reaction solution isevaporated under reduced pressure and to the resulting residue is addedwater and then extracted with ethyl acetate. The extract is washedsuccessively with diluted hydrochloric acid and saturated salinesolution, and dried over magnesium sulfate. The solvent is distilled offand the resulting residue is recrystallized from ethyl acetate/n-hexaneto give5-methanesulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.72 g) as white powder, m.p. 189°-190° C.

EXAMPLE 766

5-Methanesulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.49 g) is dissolved in a mixture (25 ml) ofacetonitrile/dimethylformamide (4:1) and thereto is added sodium azide(0.11 g). The mixture is refluxed with stirring for 3.5 hours. Aftercooling, the reaction solution is poured into ice-water (40 ml),extracted with ethyl acetate, washed with saturated saline solution, anddried over magnesium sulfate. The solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; ethyl acetate:n-hexane=1:2), and recrystallized from ethylacetate/n-hexane to give5-azidomethyl-1-[4-(2-methylbenzoylamino)benzoly]-2,3,4,5-tetrahydro-1H-benzazepine(0.29 g) as white powder, m.p. 188°-189° C.

EXAMPLE 767

5-Azidomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.27 g) is suspended in ethanol (50 ml) and the mixture is subjected tocatalytic hydrogenation at room temperature under 3 kg/cm² for 6 hoursby using 10% Pd-C (27 mg). The catalyst is removed by filtration withcelite and the filtrate is distilled off and the resulting residue isrecrystallized from ethanol to give5-aminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.12 g) as colorless needles, m.p. 233°-235° C.

EXAMPLE 768

To5,5-epoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.30 g) is added 30% solution of methylamine in methanol (30 ml), andthe mixture is refluxed for 14 hours. After compeltion of the reaction,the reaction solution is evaporated under reduced pressure and theresulting residue is purified by silica gel column chromatography(eluent; ethyl acetate:n-hexane=1:1→dichloromethane:methanol:aqueousammonia=60:10:1) to give5-hydroxymethyl-5-methylamino-1-[4-(2-methylbenzoylamino]benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(A; 35.3 mg) and5-methylaminomethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(B; 109 mg).

(A); Colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.50-2.10 (3H, m), 2.10-2.28 (1H, m), 2.36 (3H, s),2.48 (3H, s), 2.68-2.97 (1H, m), 3.26-3.47 (1H, m), 4.16 (1H, d, J=13.8Hz), 4.25 (1H, d, J=13.8 Hz), 5.95 (1H, brs), 6.60-6.76 (1H, m),6.97-7.52 (8H, m), 7.52-7.73 (2H, m), 7.73-7.97 (2H, m)

(B); White powder (recrystallized from ethyl acetate/n-hexane) m.p.176°-179° C.

EXAMPLE 769

5-Methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1 g) is dissolved in dimethylformamide (10 ml) and thereto are addedpotassium carbonate (0.5 g) and ethyl iodide (0.45 g). The mixture isstirred at room temperature overnight. After completion of the reaction,the reaction solution is poured into ice-water and the precipitatedcrystal is collected by filtration, and purified by silica gel columnchromatography (eluent; dichloromethane:methanol=90:1), andrecrystallized from diisopropyl alcohol/petroleum ether to give5-(N-methyl-N-ethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(50 mg) as white powder, m. p. 192°-193° C.

Using the suitable starting materials, the compounds of the aboveExamples 244, 246-248, 330, 339, 342, 346, 350, 366, 375, 376, 406-418,453, 455, 457, 460, 464, 467, 506, 507, 537-545, 547, 549-556, 561-566,568-571, 577, 601-603, 607-625, 654-672, 675, 677-681, 691-695, 697,698, 701-705, 707, 708, 712, 713, 715, 716, 719, 720 and 722-725 areobtained in the same manner as in Example 769.

EXAMPLE 770

To a suspension of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(3 g) in methanol (30 ml) are added potassium carbonate (1.5 g) andepichlorohydrine (5.7 ml), and the mixture is refluxed for 3 hours. Thesolvent is distilled off and to the resulting residue is added water andextracted three times with dichloromethane. The extract is washed withsaturated saline solution and dried over magnesium sulfate. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=80:1) to give5-(N-methyl-N-oxiranylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(C; 1.92 g) and5-[N-methyl-N-(2-hydroxy-3-methoxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(D; 0.38 g).

(C); Colorless needles (recrystallization from ethyl acetate) m.p.239°-240° C.

(D); Colorless amorphous ¹ H-NMR (CDCl₃) δ; 1.35-4.55 (22H, m), 6.3-7.8(13H, m)

EXAMPLE 771

5-[N-Methyl-N-oxiranylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.5 g) is dissolved in methanol (10 ml) and thereto is addeddiethylamine (0.13 ml). The mixture is refluxed for 3 hours. Aftercompletion of the reaction, the solvent is distilled off and theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=30:1→dichloromethane:methanol:aqueousammonia=9:1:0.1) to give5-[N-methyl-N-(2-hydroxy-3-diethylaminopropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.38 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.10 (6H, t, J=7 Hz), 1.35-5.1 (23H, m), 6.55-7.8(13H, m)

EXAMPLE 772

A solution of5-hydroxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.06 g) in acetic anhydride (10 ml) and pyridine (10 ml) is stirred atroom temperature overnight. After completion of the reaction, thereaction solution is concentrated. To the resulting residue is addedwater and the mixture is extracted with dichloromethane. The extract iswashed with saturated saline solution and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=80:1), and recrystallized fromethanol/petroleum ether to give5-acetyloxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.75 g) as colorless prisms, m.p. 142°-144° C.

EXAMPLE 773

Using the suitable starting materials, the compounds of the aboveExamples 671 and 672 are obtained in the same manner as in Example 380.

EXAMPLE 774

Using the suitable starting materials, the compounds of the aboveExamples 674, 699, 700, 706, 718 and are obtained in the same manner asin Example 384.

EXAMPLE 775

Using the suitable starting materials, the compounds of the aboveExamples 654-672, 675, 677-687, 691-695, 697, 698, 701-705, 707, 708,712, 713, 715, 716 and 719-725 are obtained in the same manner as inExample 390.

EXAMPLE 776

Using the suitable starting materials, the compounds of the aboveExamples 654-672, 675, 677-679, 691-693, 698, 701-705, 707, 708, 712,713, 715, 716 and 719-725 are obtained in the same manner as in Example388.

EXAMPLE 777

Using the suitable starting materials, the compounds of the aboveExamples 705, 706 and 708 are obtained in the same manner as in Example394.

EXAMPLE 778

Using the suitable starting materials, the compound of the above Example671 is obtained in the same manner as in Example 397.

EXAMPLE 779

Using the suitable starting materials, the compound of the above Example672 is obtained in the same manner as in Example 402.

EXAMPLE 780

Using the suitable starting materials, the compound of the above Example726 is obtained in the same manner as in Example 634.

EXAMPLE 781

Using the suitable starting materials, the compound of the above Example740 is obtained in the same manner as in Examples 638 and 640.

EXAMPLE 782

Using the suitable starting materials, the compound of the above Example689 is obtained in the same manner as in Example 643.

EXAMPLE 783

Using the suitable starting materials, the compound of the above Example690 is obtained in the same manner as in Example 644.

EXAMPLE 784

Using the suitable starting materials, the following compound isobtained in the same manner as in Examples 1, 382, 388 and 390.

5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride, colorless needles (recrystallized from ethanol/water),m.p. 233°-237° C.

REFERENCE EXAMPLE 13

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-(2-Chloroacetyloxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 156°-159° C. (recrystallized from ethylacetate/n-hexane)

5-(2-Dimethylaminoacetyloxy)-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 108°-109° C. (recrystallized from ethylacetate/n-hexane)

5-Oxo-7-chloro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 157.5°-159.5° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-8-chloro-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 151.5°-153.5° C. (recrystallized from diethylether/dichloromethane)

REFERENCE EXAMPLE 14

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-(2-Dimethylaminoacetyloxy)-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.63-1.98 (2H, m), 1.98-2.25 (1H, m), 2.27 (3H, s),2.43 (3H, s), 2.65-3.23 (2H, m), 3.38 (2H, s), 3.67 (2H, brs), 4.77-5.28(1H, m), 6.04-6.31 (1H, m), 6.31-6.56 (2H, m), 6.58-6.86 (1H, m),6.86-7.46 (5H, m)

5-Oxo-7-chloro-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 193°-193.5° C. (recrystallized from diethylether/dichloromethane)

5-Oxo-8-chloro-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 171°-174° C. (recrystallized from diethylether/dichloromethane)

REFERENCE EXAMPLE 15

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

5-Dimethylaminocarbonylmethoxy-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 129°-131° C. (recrystallized from ethylacetate/n-hexane)

6-Oxo-1-(4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, yellowneedles

¹ H-NMR (CDCl₃) δ; 1.65-2.3 (4H, m), 2.5-5.2 (4H, m), 6.7-6.9 (1H, m),7.27-7.5 (4H, m), 7.90-8.15 (3H, m)

6-Chloro-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 198°-202° C. (recrystallized fromdichloromethane/diethyl ether)

REFERENCE EXAMPLE 16

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

5-Dimethylaminocarbonylmethoxy-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.52-2.10 (3H, m), 2.10-3.20 (2H, m), 2.97 (3H, s),3.05 (3H, s), 4.03-4.48 (2H, m), 4.50-5.35 (2H, m), 6.26-6.57 (2H, m),6.57-6.88 (1H, m), 6.88-7.76 (5H, m)

6-Oxo-1-(4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine, light yellowamorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.2 (4H, m), 2.5-5.2 (6H, m), 6.42 (2H, d, J=8.7Hz), 6.75-6.9 (1H, m), 7.05-7.4 (4H, m), 7.95-8.1 (1H, m)

6-Chloro-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 166°-169° C. (recrystallized fromdichloromethane/diethyl ether)

9-Chloro-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder, m.p. 192.5°-195° C. (recrystallized fromdichloromethane/diethyl ether)

REFERENCE EXAMPLE 17

5-Dimethylamino-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(86.0 g) is dissolved in ethanol (800 ml), and thereto is added platinumoxide (10 g). The mixture is subjected to hydrogenation at ordinarytemperature under atmospheric pressure of hydrogen for 4 hours. Thecatalyst is removed by filtration, and the solvent is distilled off. Theresulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol=200:1→100:1), and further purified bysilica gel thin layer chromatography (developer; chloroform:methanol=10:1), and recrystallized from methanol/diethyl ether to give5-dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(G) (Rf:0.52, 27.4 g) and5-dimethylamino-1-(2-methyl-4-amino-benzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(H) (Rf:0.48, 12.3 g).

(G): White powder

M.p. 154°-156° C.

[α]²² _(D) =0° (c=1.0, chloroform)

¹ H-NMR (CDCl₃) δ; 1.10-1.50 (1H, m), 1.50-2.00 (1H, m), 2.00-2.35 (11H,m), 2.90-5.18 (5H, m), 6.00-6.76 (3H, m), 6.81-7.64 (4H, m)

(H) White powder

M.p. 169.5°-170° C.

[α]²² _(D) =0° (c=1.5, chloroform)

¹ H-NMR (CDCl₃) δ; 1.11-2.90 (13H, m), 2.91-5.23 (5H, m), 6.15-6.53 (1H,m), 6.57-7.62 (6H, m)

Using the suitable starting materials, the compounds of the followingTable 5 are obtained in the same manner as in above Examples 1 and 382.##STR782##

EXAMPLE 785 ##STR783## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol Melting Point: 174°-175° C. Form:Free EXAMPLE 786 ##STR784## Crystalline form: Colorless prismsRecrystallization solvent: Ethanol/diethyl ether Melting Point: 176-178° C. Form: Free EXAMPLE 787 ##STR785## Crystalline form: Colorlessprisms Recrystallization solvent: Ethyl acetate/petroleum ether MeltingPoint: 154.5°-155° C. Form: Free EXAMPLE 788 ##STR786## Crystallineform: Colorless amorphous NMR analysis: 138) Form: Free EXAMPLE 789##STR787## Crystalline form: Colorless scales Recrystallization solvent:Ethanol Melting Point: 197°-198° C. Form: Free EXAMPLE 790 ##STR788##Crystalline form: Colorless needles Recrystallization solvent: EthanolMelting Point: 248°-249° C. Form: Free EXAMPLE 791 ##STR789##Crystalline form: Colorless needles Recrystallization solvent:Ethanol/n-hexane Melting Point: 162°-163° C. Form: Free EXAMPLE 792##STR790## Crystalline form: Colorless prisms Recrystallization solvent:Ethanol/petroleum ether Melting Point: 235°-236.5° C. Form: Free EXAMPLE793 ##STR791## Crystalline form: Colorless amorphous NMR analysis: 139)Form: Free EXAMPLE 794 ##STR792## Crystalline form: Colorless prismsRecrystallization solvent: Dioxane Melting Point: 269°-271° C. Form:Free EXAMPLE 795 ##STR793## Crystalline form: Colorless prismsRecrystallization solvent: Dimethylformamide Melting Point: 286°-287° C.Form: Free EXAMPLE 796 ##STR794## Crystalline form: Colorless needlesRecrystallization solvent: Acetonitrile Melting Point: 227°-228° C.Form: Free EXAMPLE 797 ##STR795## Crystalline form: Colorless amorphousNMR analysis: 140) Form: Free EXAMPLE 798 ##STR796## Crystalline form:Colorless prisms Recrystallization solvent: Ethyl acetate/petroleumether Melting Point: 167°-168° C. Form: Free EXAMPLE 799 ##STR797##Crystalline form: Colorless amorphous NMR analysis: 141) EXAMPLE 800##STR798## Crystalline form: Colorless needles Recrystallizationsolvent: Diethyl ether Melting Point: 164°-171° C. Form: K.sup.⊕ EXAMPLE801 ##STR799## Crystalline form: Colorless amorphous NMR analysis: 142)Form: Free EXAMPLE 802 ##STR800## Crystalline form: Colorless amorphousNMR analysis: 143) Form: Free EXAMPLE 803 ##STR801## Crystalline form:Colorless amorphous NMR analysis: 144) Form: Free EXAMPLE 804 ##STR802##Crystalline form: Colorless amorphous NMR analysis: 145) Form: FreeEXAMPLE 805 ##STR803## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol Melting Point: 207°-208° C. Form:Free EXAMPLE 806 ##STR804## Crystalline form: White powderRecrystallization solvent: Dichloromethane/diethyl ether Melting Point:187°-189° C. Form: Free EXAMPLE 807 ##STR805## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol/petroleum etherMelting Point: 217°-218° C. Form: Free EXAMPLE 808 ##STR806##Crystalline form: Colorless needles Recrystallization solvent: Ethylacetate Melting Point: 170°-171° C. Form: Free EXAMPLE 809 ##STR807##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 239.5°-241° C. Form: Free EXAMPLE 810 ##STR808##Crystalline form: Colorless needles Recrystallization solvent: EthanolMelting Point: 190°-191° C. Form: Free EXAMPLE 811 ##STR809##Crystalline form: Colorless prisms Recrystallization solvent: Diethylether Melting Point: 163°-163.5° C. Form: Free EXAMPLE 812 ##STR810##Crystalline form: Colorless prisms Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 208°-210° C. Form: Free EXAMPLE 813##STR811## Crystalline form: White powder NMR analysis: 146) Form: FreeEXAMPLE 814 ##STR812## Crystalline form: Colorless amorphous NMRanalysis: 147) Form: Free EXAMPLE 815 ##STR813## Crystalline form:Colorless needles Recrystallization solvent: Ethanol/n-hexane MeltingPoint: 250°-252° C. Form: Free EXAMPLE 816 ##STR814## Crystalline form:Colorless prisms Recrystallization solvent: Ethyl acetate Melting Point:214°-216° C. Form: Free EXAMPLE 817 ##STR815## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol/n-hexane MeltingPoint: 243°-245° C. Form: Free EXAMPLE 818 ##STR816## Crystalline form:Colorless prisms Recrystallization solvent: Diethyl ether Melting Point:159°-162° C. Form: Free EXAMPLE 819 ##STR817## Crystalline form:Colorless amorphous NMR analysis: 148) Form: Free EXAMPLE 820 ##STR818##Crystalline form: Colorless prisms Recrystallization solvent: Ethylacetate Melting Point: 287°-289° C. Form: Free EXAMPLE 821 ##STR819##Crystalline form: Colorless prisms Recrystallization solvent: Diethylether Melting Point: 170°-171° C. Form: Free EXAMPLE 822 ##STR820##Crystalline form: White powder Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 204°-205° C. Form: Free EXAMPLE 823##STR821## Crystalline form: White powder Recrystallization solvent:Ethyl acetate/n-hexane Melting Point: 273°-273.5° C. Form: Free EXAMPLE824 ##STR822## Crystalline form: Colorless amorphous NMR analysis: 149)Form: Free EXAMPLE 825 ##STR823## Crystalline form: White powderRecrystallization solvent: Ethyl acatete/n-hexane Melting Point:240°-241° C. Form: Free EXAMPLE 826 ##STR824## Crystalline form: Whitepowder Recrystallization solvent: Acetonitrile/ethanol Melting Point:231°-232° C. Form: Free EXAMPLE 827 ##STR825## Crystalline form: Whitepowder Recrystallization solvent: Acetonitrile/ethanol Melting Point:222°-224° C. Form: Free EXAMPLE 828 ##STR826## Crystalline form: Whitepowder Recrystallization solvent: Ethyl acetate/n-hexane Melting Point:235°-237° C. Form: Free EXAMPLE 829 ##STR827## Crystalline form:Colorless amorphous NMR analysis: 150) Form: Free EXAMPLE 830 ##STR828##Crystalline form: Colorless amorphous NMR analysis: 151) Form: FreeEXAMPLE 831 ##STR829## Crystalline form: Colorless amorphous NMRanalysis: 152) Form: Free EXAMPLE 832 ##STR830## Crystalline form:Colorless amorphous NMR analysis: 153) Form: Free EXAMPLE 834 ##STR831##Crystalline form: White powder Recrystallization solvent: Ethylacetate/n-hexane Melting Point: 247°-248° C. Form: Free EXAMPLE 835##STR832## Crystalline form: Colorless amorphous NMR analysis: 154)Form: Free EXAMPLE 836 ##STR833## Crystalline form: Colorless amorphousNMR analysis: 155) Form: Free EXAMPLE 837 ##STR834## Crystalline form:Colorless amorphous NMR analysis: 156) Form: Free EXAMPLE 838 ##STR835##Crystalline form: Colorless amorphous NMR analysis: 157) Form: FreeEXAMPLE 839 ##STR836## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 234°-235° C. Form: FreeEXAMPLE 840 ##STR837## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 234°-235° C. Form: FreeEXAMPLE 841 ##STR838## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 226°-228° C. Form: FreeEXAMPLE 842 ##STR839## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 230°-231° C. Form: FreeEXAMPLE 843 ##STR840## Crystalline form: White powder Recrystallizationsolvent: Ethyl acetate/n-hexane Melting Point: 186°-188° C. Form: FreeEXAMPLE 844 ##STR841## Crystalline form: Colorless prismsRecrystallization solvent: Chloroform/methanol Melting Point: 286°-290°C. Form: Free EXAMPLE 845 ##STR842## Crystalline form: Colorless needlesRecrystallization solvent: Ethanol Melting Point: 186°-188.5° C. Form:Free EXAMPLE 846 ##STR843## Crystalline form: Colorless prismsRecrystallization solvent: Ethanol Melting Point: 220°-222° C. Form:Free EXAMPLE 847 ##STR844## Crystalline form: White powder NMR analysis:158) Form: Free EXAMPLE 848 ##STR845## Crystalline form: Colorlessprisms Recrystallization solvent: Dichloromethane/diethyl ether MeltingPoint: 189°-192° C. Form: Free EXAMPLE 849 ##STR846## Crystalline form:Colorless amorphous NMR analysis: 159) Form: Free EXAMPLE 850 ##STR847##Crystalline form: White powder Recrystallization solvent:Dichloromethane/diethyl ether Melting Point: 207°-209° C. (decomposed)Form: Free EXAMPLE 851 ##STR848## Crystalline form: White powder NMRanalysis: 160) Form: K.sup.⊕ EXAMPLE 852 ##STR849## Crystalline form:White powder Recrystallization solvent: Dichloromethane/diethyl etherMelting Point: 193°-194° C. Form: Free EXAMPLE 853 ##STR850##Crystalline form: White powder Recrystallization solvent: Diethylether/dichloromethane Melting Point: 185.5°-186° C. Form: Free EXAMPLE854 ##STR851## Crystalline form: White powder Recrystallization solvent:Diethyl ether/dichloromethane Melting Point: 223.5°-226° C. (decomposed)Form: Free EXAMPLE 855 ##STR852## Crystalline form: Colorless amorphousNMR analysis: 161) Form: Free EXAMPLE 856 ##STR853## Crystalline form:White powder Recrystallization solvent: Diethyl ether/dichloromethaneMelting Point: 225.5°-227° C. Form: Free EXAMPLE 857 ##STR854##Crystalline form: White powder Recrystallization solvent: Diethylether/dichloromethane Melting Point: 212°-214° C. Form: Free EXAMPLE 858##STR855## Crystalline form: White powder Recrystallization solvent:Diethyl ether/dichloromethane Melting Point: 230.5°-233° C. Form: FreeEXAMPLE 859 ##STR856## Crystalline form: White powder Recrystallizationsolvent: Diethyl ether/dichloromethane Melting Point: 212.5°-215° C.(decomposed) Form: Free EXAMPLE 860 ##STR857## Crystalline form: Whitepowder Recrystallization solvent: Diethyl ether/dichloromethane MeltingPoint: 192°-194.5° C. Form: Free EXAMPLE 861 ##STR858## Crystallineform: White powder Recrystallization solvent: Diethylether/dichloromethane Melting Point: 175°-177° C. Form: Free EXAMPLE 862##STR859## Crystalline form: White powder Recrystallization solvent:Diethyl ether/dichloromethane Melting Point: 208.5°-209.5° C. Form: FreeEXAMPLE 863 ##STR860## Crystalline form: White powder Recrystallizationsolvent: Diethyl ether/dichloromethane Melting Point: 191°-193.5° C.Form: Free EXAMPLE 864 ##STR861## Crystalline form: White powderRecrystallization solvent: Diethyl ether/dichloromethane Melting Point:204°-205.5° C. Form: Free EXAMPLE 865 ##STR862## Crystalline form: Lightyellow prisms Recrystallization solvent: Ethanol Melting Point:221°-223° C. Form: Free EXAMPLE 866 ##STR863## Crystalline form:Colorless prisms Recrystallization solvent: Ethyl acetate Melting Point:171°-173° C. Form: Free EXAMPLE 867 ##STR864## Crystalline form:Colorless prisms Recrystallization solvent: Ethyl acetate Melting Point:185°-187° C. Form: Free EXAMPLE 868 ##STR865## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol Melting Point:190°-192° C. Form: Free EXAMPLE 869 ##STR866## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol Melting Point:175-177° C. Form: Free EXAMPLE 870 ##STR867## Crystalline form:Colorless powder Recrystallization solvent: Ethyl acetate/n-hexaneMelting Point: 148°-151° C. Form: Free EXAMPLE 871 ##STR868##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 200°-202° C. Form: Free EXAMPLE 872 ##STR869##Crystalline form: Colorless prisms Recrystallization solvent: EthanolMelting Point: 200°-202° C. Form: Free EXAMPLE 873 ##STR870##Crystalline form: Light yellow powder Recrystallization solvent: AcetoneMelting Point: 235°-238° C. Form: Free EXAMPLE 874 ##STR871##Crystalline form: Light yellow powder Recrystallization solvent: AcetoneMelting Point: 198°-201° C. Form: Free EXAMPLE 875 ##STR872##Crystalline form: Light yellow needles Recrystallization solvent:Chloroform/ethyl acetate Melting Point: 232°-237° C. Form: Free EXAMPLE876 ##STR873## Crystalline form: Colorless prisms Recrystallizationsolvent: Chloroform/ethyl acetate Melting Point: 224°-227° C. Form: FreeEXAMPLE 877 ##STR874## Crystalline form: Colorless prismsRecrystallization solvent: Ethanol Melting Point: 211°-214° C. Form:Free EXAMPLE 878 ##STR875## Crystalline form: Colorless powderRecrystallization solvent: Dichloromethane/n-hexane Melting Point:238°-243° C. Form: Free EXAMPLE 879 ##STR876## Crystalline form:Colorless amorphous NMR analysis: 162) Form: Free EXAMPLE 880 ##STR877##Crystalline form: Colorless amorphous NMR analysis: 163) Form: FreeEXAMPLE 881 ##STR878## Crystalline form: Colorless prismsRecrystallization solvent: Dichloromethane/diethyl ether Melting Point:198°-202° C. Form: Free EXAMPLE 882 ##STR879## Crystalline form:Colorless prisms Recrystallization solvent: Chloroform/ethyl acetateMelting Point: 226°-229° C. Form: Free EXAMPLE 883 ##STR880##Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 139°-140° C. Form: Free EXAMPLE884 ##STR881## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 149°-152° C. Form: Free EXAMPLE885 ##STR882## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 180.5°-182° C. Form: Free EXAMPLE886 ##STR883## Crystalline form: White powder Recrystallization solvent:Chloroform/diethyl ether Melting Point: 211°-214° C. Form: Free EXAMPLE887 ##STR884## Crystalline form: White powder Recrystallization solvent:Chloroform/diethyl ether Melting Point: 171°-174.5° C. Form: FreeEXAMPLE 888 ##STR885## Crystalline form: White powder Recrystallizationsolvent: Methanol/diethyl ether Melting Point: 203°-205° C. Form: FreeEXAMPLE 889 ##STR886## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 202-202.5 Form: Free EXAMPLE 890##STR887## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 130°-133° C. Form: Free EXAMPLE891 ##STR888## Crystalline form: White powder Recrystallization solvent:Methanol/n-hexane Melting Point: 104.5°-106° C. Form: Free EXAMPLE 892##STR889## Crystalline form: White powder Recrystallization solvent:Methanol/diethyl ether Melting Point: 197°-198° C. Form: Free EXAMPLE893 ##STR890## Crystalline form: White powder Recrystallization solvent:Dichloromethane/ethyl acetate Melting Point: 191°-192° C. Form: FreeEXAMPLE 894 ##STR891## Crystalline form: Colorless columnarRecrystallization solvent: Ethanol/petroleum ether Melting Point:211°-213° C. Form: Free EXAMPLE 895 ##STR892## Crystalline form:Colorless amorphous NMR analysis: 164) Form: Free EXAMPLE 896 ##STR893##Crystalline form: Colorless amorphous NMR analysis: 165) Form: FreeEXAMPLE 897 ##STR894## Crystalline form: Colorless amorphous NMRanalysis: 166) Form: Free EXAMPLE 898 ##STR895## Crystalline form:Colorless prisms Recrystallization solvent: Ethanol Melting Point:224°-228° C. Form: Free

138) ¹ H-NMR (CDCl₃) δ; 1.3-2.95 (19H, m), 3.05-3.3 (1H, m), 3.85-4.1(2H, m), 4.3-4.6 (1H, 6.64 (1H, d, J=7.8 Hz), 6.9-7.8 (12H, m)

139) ¹ H-NMR (CDCl₃) δ; 1.1-2.3 (13H, m), 2.65-3.2 (1H, m), 4.55-5.6(3H, m), 6.55-6.7 (1H, m), 6.9-7.6 (12H, m)

140) ¹ H-NMR (CDCl₃) δ; 1.3-4.15 (19H, m), 4.3-5.0 (1H, m), 6.65 (1H, d,J=7.7 Hz), 6.9-8.05 (12H, m) 141) ¹ H-NMR (CDCl₃) δ; 1.4-3.0 (9H, m),3.05-3.6 (3H, m), 3.9-4.1 (1H, m), 4.35-4.55 (1H, m), 4.9-5.65 (1H, m),6.67 (1H, d, J=7.4 Hz), 6.85-7.6 (12H, m), 7.6-7.85 (2H, m)

142) ¹ H-NMR (CDCl₃) δ; 1.3-2.85 (21H, m), 3.2-4.0 (4H, m), 4.3-4.4 (1H,m), 4.45-5.2 (2H, m), 6.61 (1H, d, J=7.6 Hz), 6.9-7.65 (12H, m)

143) ¹ H-NMR (CDCl₃) δ; 1.3-3.45 (17H, m), 3.8-5.7 (5H, m), 6.5-7.65(13H, m)

144) ¹ H-NMR (CDCl₃) δ; 1.25-3.1 (14H, m), 3.3-4.0 (4H, m), 4.15-4.4(1H, 4.45-5.2 (1H, m), 6.64 (1H, d, J=7.4 Hz), 6.9-7.7 (12H, m)

145) ¹ H-NMR (CDCl₃) δ; 0.9-3.25 (16H, m), 3.9-5.9 (2H, m), 6.65 (1H, d,J=7.4 Hz), 6.85-7.5 (11H, m), 7.9-8.3 (1H, m)

146) ¹ H-NMR (DMSO-d₆) δ; 1.3-2.15 (4H, m), 2.32 (3H, s), 2.8-3.05 (1H,m), 4.24 (2H, AB-q, J=12.8, 15.4 Hz), 4.35-4.55 (1H, m), 4.9-5.25 (1H,m), 6.68 (1H, d, J=7.6 Hz), 6.9-7.45 (9H, m), 7.52 (2H, d, J=8.6 Hz),8.9-9.05 (1H, m), 10.31 (1H, s)

147) ¹ H-NMR (CDCl₃) δ; 1.5-2.35 (4H, m), 2.45 (3H, s), 2.6-2.85 (1H,m), 3.32 (3H, s), 4.19 (2H, AB-q, J=12.2 Hz, 15.6 Hz), 5.0-5.2 (1H, m),5.82 (1H, d, J=10.3 Hz), 6.69 (1H, d, J=7.8 Hz), 6.75-7.95 (12H, m)

148) ¹ H-NMR (CDCl₃) δ; 1.2-3.3 (17H, m), 3.45 (2H, AB-q, J=14.7, 22.9Hz), 3.9-4.35 (2H, m), 6.60 (2H, d, J=7.7 Hz), 6.8-8.0 (11H, m), 8.39(1H, s)

149) ¹ H-NMR (CDCl₃) δ; 1.45-3.40 (8H, m), 2.23 (3H, s), 2.33 (3H, s),2.46 (3H, s), 4.44-5.23 (1H, m), 6.54-6.78 (1H, m), 6.84-7.94 (12H, m)

150) ¹ H-NMR (CDCl₃) δ; 1.50-1.92 (3H, m), 1.92-2.05 (1H, m), 2.47 (3H,s), 2.55-3.06 (5H, m), 3.43-5.76 (8H, m), 6.63-6.82 (1H, m), 6.97-8.08(12H, m)

151) ¹ H-NMR (CDCl₃) δ; 1.43-2.65 (4H, m), 2.48 (3H, s), 2.69-3.25 (5H,m), 3.90-5.40 (8H, m), 6.64-6.94 (1H, m), 6.94-7.77 (12H, m)

152) ¹ H-NMR (CDCl₃) δ; 1.50-1.90 (3H, m), 1.90-2.20 (1H, m), 2.20-2.64(4H, m), 2.32 (3H, s), 2.47 (3H, s), 2.64-3.27 (1H, m), 3.36-3.83 (4H,m), 3.93-4.52 (2H, m), 4.52-5.27 (2H, m), 6.57-6.82 (1H, m), 6.93-7.87(12H, m)

153) ¹ H-NMR (CDCl₃) δ; 1.52-1.93 (2H, m), 1.93-2.23 (4H, m), 2.23-2.57(1H, m), 2.45 (3H, s), 2.72-3.02 (1H, m), 3.02-3.77 (8H, m), 3.93-4.50(2H, m), 4.50-5.20 (2H, m), 6.60-6.80 (1H, m), 6.94-7.64 (11H, m), 8.16(1H, brs)

154) ¹ H-NMR (CDCl₃) δ; 1.48-2.60 (8H, m), 2.46 (3H, s), 2.65-3.01 (1H,m), 3.20-3.74 (2H, m), 3.80-5.14 (4H, m), 5.30-5.84 (1H, m), 6.51-8.14(13H, m)

155) ¹ H-NMR (CDCl₃) δ; 1.54-1.91 (2H, m), 1.91-2.20 (1H, m), 2.22-2.64(1H, m), 2.44 (3H, s), 2.70-3.13 (1H, m), 3.60-4.40 (4H, m), 4.50-5.20(2H, m), 6.07-8.00 (13H, m), 9.93 (1H, s)

156) ¹ H-NMR (CDCl₃) δ; 1.56-1.92 (2H, m), 1.92-2.19 (1H, m), 2.19-2.60(1H, m), 2.46 (3H, s), 2.66-3.26 (4H, m), 3.33-3.95 (4H, m). 4.00-5.20(4H, m), 6.58-6.82 (1H, m), 6.93-8.21 (12H, m)

157) ¹ H-NMR (CDCl₃) δ; 1.57-2.17 (3H, m), 2.21-2.68 (1H, m), 2.47 (3H,s), 2.73-3.04 (1H, m), 3.91-4.42 (4H, m), 4.50-5.17 (2H, m), 6.61-6.99(2H, m), 6.99-8.10 (14H, m), 8.21-8.71 (2H, m)

158) ¹ H-NMR (CDCl₃) δ; 1.31 (3H, d, J=6.7 Hz), 1.53-1.90 (1H, m),2.29-2.58 (1H, m), 2.47 (3H, s), 2.94-3.63 (2H, m), 4.57-5.05 (1H, m),6.68-6.82 (1H, m), 7.10-7.59 (10H, m), 7.72 (1H, s), 7.78-7.96 (1H, m)

159) ¹ H-NMR (CDCl₃) δ; 1.20-2.60 (17H, m), 2.65-5.10 (3H, m), 6.85-3.85(12H, m)

160) ¹ H-NMR (DMSO-d₆) δ; 1.40-1.75 (1H, m), 1.90-2.15 (1H, m), 2.33(3H, s), 2.50-2.80 (2H, m), 3.10-3.50 (1H, m), 4.40-4.65 (1H, m),6.85-7.60 (10H, m), 7.85 (1H, s), 10.44 (1H, s)

161) ¹ H-NMR (CDCl₃) δ; 1.30-2.70 (11H, m), 3.00-5.20 (3H, m), 6.58 (1H,d, J=8 Hz), 6.90-7.05 (1H, m), 7.10-7.70 (10H, m)

162) ¹ H-NMR (CDCl₃) δ; 1.25-2.90 (4H, m), 2.44 (6H, s), 2.79-3.57 (2H,m), 2.79 (6H, s), 4.10-5.25 (1H, m), 6.60-6.80 (1H, m), 6.94-7.60 (10H,m), 8.23 (1H, d, J=6.2 Hz), 12.41 (1H, m)

163) ¹ H-NMR (CDCl₃) δ; 1.25-3.00 (4H, m), 2.42 (6H, s), 2.99 (6H, s),3.40-3.65 (2H, m), 4.01-5.15 (1H, m), 6.58-7.59 (12H, m), 7.94 (1H, brs)

164) ¹ H-NMR (DMSO-d₆) δ; 1.40-2.18 (4H, m), 2.34 (3H, s), 2.47 (3H, s),2.54-3.50 (4H, m), 4.30-5.08 (1H, m), 6.56-6.82 (1H, m), 6.87-7.48 (10H,m), 7.48-7.75 (2H, m), 10.35 (1H, s)

165) ¹ H-NMR (CDCl₃) δ; 1.08-5.20 [20H, m, 1.30 (3H, t, J=7.2 Hz), 3.41(2H, s), 4.22 (2H, q, J=7.2 Hz)], 6.49-7.73 (8H, m), 9.25-9.58 (1H, m)

166) ¹ H-NMR (CDCl₃) δ; 1.17-2.80 (4H, m), 2.05 (3H, s), 2.42 (6H, s),3.02-3.53 (2H, m), 4.06-5.15 (1H, m), 6.55-7.80 (12H, m), 8.53-8.74 (2H,m)

EXAMPLE 899

To a solution of5-acetyloxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.48 g) in acetic acid (20 ml) is added platinum oxide (0.05 g) and themixture is subjected to catalytic reduction under hydrogen atmosphere.After completion of the reaction, the catalyst is removed by filtration,and the filtrate is concentrated. The resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=20:1→10:1), and recrystallized fromethanol/diethyl ether to give5-amino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.19 g) as colorless prisms, m.p. 176°-178° C.

EXAMPLE 900

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane (10 ml) is added triethylamine (0.24 ml).Subsequently, thereto is added methanesulfonyl chloride (0.14 ml) underice-cooling, and then, the mixture is warmed to room temperature andstirred overnight. Water is added to the reaction solution, extractedthree times with dichloromethane. The extract is washed with saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=20:1), andrecrystallized from ethanol to give5-(N-methyl-N-methanesulfonylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.48 g) as colorless scales, m.p. 197°-198° C.

EXAMPLE 901

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane is added triethylamine (0.24 ml).Subsequently, thereto is added benzoyl chloride (0.2 ml) underice-cooling, and the temperature thereof is raised to room temperature,and the mixture is stirred overnight. Water is added to the reactionsolution and extracted three times with dichloromethane. The extract iswashed with saturated saline solution and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=20:1), and recrystallized from ethanol to give5-(N-methyl-N-benzoylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.64 g) as colorless needles, m.p. 248°-249° C.

EXAMPLE 902

A mixture of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) and ethyl formate (10 ml) is refluxed for 4 hours. The reactionsolution is concentrated and the resulting residue is recrystallizedfrom ethanol/petroleum ether to give5-formylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.38 g) as colorless columnar crystal, m.p. 211°-213° C.

Using the suitable starting materials, the compounds of above Examples825 and 894 are obtained in the same manner as in above Example 902.

Example 903

To a solution of5-amino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane (10 ml) is added triethylamine (0.22 ml).Subsequently, thereto is added di-tert-butyl dicarbonate (0.34 g) atroom temperature and the mixture is stirred for 2 hours. Then, theretois added additional di-tert-butyl dicarbonate (0.1 g) and the mixture isstirred for 1 hour. The reaction mixture is concentrated and theresulting residue is purified by silica gel column chromatography(eluent; n-hexane:ethyl aceate=1:1) to give5-t-butoxycarbonylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.66 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.1-2.3 (13H, m), 2.65-3.2 (1H, m), 4.55-5.6 (3H, m),6.55-6.7 (1H, m), 6.9-7.6 (12H, m)

Using the suitable starting materials, the compound of above Example 791is obtained in the same manner as in above Example 903.

EXAMPLE 904

To a solution of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dichloromethane (10 ml) is added phenyl isocyanate (0.2 g)under ice-cooling. The mixture is stirred at the same temperature for 30minutes, and the temperature thereof is raised to room temperature andthen the mixture is stirred overnight. The reaction solution isdistilled off and the resulting residue is recrystallized from dioxaneto give5-anilinocarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]02,3,4,5-tetrahydro-1H-benzazepine(0.65 g) as colorless prisms, m.p. 269°-271° C.

Using the suitable starting materials, the compound of above Example 795is obtained in the same manner as in above Example 904.

EXAMPLE 905

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in methanol (10 ml) is added glycolonitrile (50%, 0.19 ml) andthe mixture is stirred at room temperature for 20 minutes, and thenrefluxed for 30 minutes. Thereto is added additional glycolonitrile (0.5ml) and the mixture is refluxed for 5.5 hours. The reaction solution isconcentrated and to the resulting residue is added ethyl acetate. Theprecipitated crystal is collected by filtration, and recrystallized fromacetonitrile to give5-(N-methyl-N-cyanomethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.32 g) as colorless needles, m.p. 227°-228° C.

EXAMPLE 906

To5-(N-methyl-N-oxiranylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.62 g) is added trifluoroacetic acid (1.22 ml) under ice-cooling andthe mixture is stirred for 4 hours. The reaction solution is neutralizedwith aqueous sodium carbonate solution, and extracted three times withdichloromethane. The extract is washed with saturated saline solutionand dried over magnesium sulfate. The solvent is distilled off and theresulting residue is dissolved in methanol (10 ml). Thereto is added 40%aqueous sodium hydroxide solution (10 ml) and water (10 ml), and themixture is stirred at room temperature overnight. Methanol is distilledoff and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=30:1) to give5-[N-methyl-N-(2,3-dihydroxypropyl)amino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.23 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.3-4.15 (19H, m), 4.3-5.0 (1H, m), 6.65 (1H, d,J=7.7 Hz), 6.9-8.05 (12H, m)

EXAMPLE 907

A mixture of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.64 g), acetonitrile (20 ml), potassium carbonate (0.6 g) and ethylbromoacetate (0.44 ml) is refluxed for 3 hours. The reaction solution isconcentrated and water is added to the resulting residue, and themixture is extracted three times with dichloromethane. The extract iswashed with saturated saline solution, and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent;dichloromethane:methanol=30:1), and recrystallized from ethylacetate/petroleum ether to give5-(N-methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.82 g) as colorless prisms, m.p. 167°-168° C.

Using the suitable starting materials, the compounds of above Examples785, 787, 799, 800, 802-806, 808, 811, 819, 824, 826, 827, 845, 848,849, 850, 852, 855-858, 860, 861, 863-882, 885-893 and 895-898 areobtained in the same manner as in above Example 907.

EXAMPLE 908

5-(N-Methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) is dissolved in saturated solution of ammonia in methanol (20ml), and the mixture is heated at 100° C. for 8 hours in a sealed tube.The reaction solution is concentrated and the resulting residue ispurified by silica gel column chromatography (eluent;dichloromethane:methanol=30:1) to give5-(N-methyl-N-carbamoylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.4 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.4-3.0 (9H, m), 3.05-3.6 (3H, m), 3.9-4.1 (1H, m),4.35-4.55 (1H, m), 4.9-5.65 (1H, m), 6.67 (1H, d, J=7.4 Hz), 6.85-7.6(12H, m), 7.6-7.85 (2H, m)

EXAMPLE 909

To a solution of5-(N-methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dioxane (10 ml) is added aqueous solution (1 ml) of sodiumhydroxide (0.07 g) and the mixture is stirred at room temperature for 2days. The reaction solution is concentrated and to the resulting residueis added water. The insoluble materials are removed by filtration. Thefiltrate is neutralized with 10% hydrochloric acid and extracted threetimes with dichloromethane. The extract is washed with saturated salinesolution and dried over magnesium sulfate. The solvent is distilled offand to the resulting residue is added a solution of potassiumethylhexanoate (0.2 g) in dichloromethane (20 ml). The solvent isdistilled off, and diethyl ether is added to the resulting residue. Theprecipitated crystal is collected by filtration, and recrystallized fromdiethyl ether to give potassium2-[N-methyl-N-{1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}amino]acetate(0.6 g) as colorless needles, m.p. 164°-171° C.

EXAMPLE 910

To a solution of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.5 g) in dimethyformamide (20 ml) are added potassium carbonate (0.6g), potassium iodide (0.72 g) and2-(3-bromopropyloxy)-3,4,5,6-tetrahydro-2H-pyrane (0.97 g) and themixture is stirred at room temperature overnight. The reaction solutionis concentrated and to the resulting residue is added water. The mixtureis extracted three times with dichloromethane. The extract is washedwith saturated saline solution, and dried over magnesium sulfate. Thesolvent is distilled off and the resulting residue is purified by silicagel column chromatography (eluent;dichloromethane→dichloromethane:methanol=50:1) to give5-(N-methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin6(1.3 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.3-2.85 (21H, m), 3.2-4.0 (4H, m), 4.3-4.4 (1H, m),4.45-5.2 (2H, m), 6.61 (1H, d, J=7.6 Hz), 6.9-7.65 (12H, m)

EXAMPLE 911

To5-{N-methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.4 g) is added a mixture of acetyl chloride (0.5 ml) and acetic acid(5 ml) at room temperature, and the mixture is stirred overnight. Thereaction solution is concentrated and the resulting residue is purifiedby silica gel column chromatography (eluent;dichloromethane:methanol=30:1), and further purified again by silica gelcolumn chromatography (eluent; n-hexane:ethyl acetate=1:2) to give5-[N-methyl-N-(3-acetyloxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.06 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.3-3.45 (17H, m), 3.8-5.7 (5H, m), 6.5-7.65 (13H, m)

EXAMPLE 912

To a solution of5-(N-methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.55 g) in ethanol (10 ml) is added pyridinium p-toluenesulfonate (0.03g) and the mixture is heated at 60° C. overnight. After the mixture isrefluxed for more 2 hours, water and pyridinium p-toluenesulfonate (0.03g) are added thereto. The mixture is refluxed for 4 hours. The reactionsolution is concentrated and to the resulting residue is addeddichloromethane. The mixture is basified with aqueous sodium hydrogencarbonate solution and extracted three times with dichloromethane. Theextract is washed with saturated saline solution and dried overmagnesium sulfate. The solvent is distilled off and the resultingresidue is purified by silica gel column chromatography (eluent;dichloromethane:methanol=30 :1) to give5-IN-methyl-N-(3-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.26 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.25-3.1 (14H, m), 3.3-4.0 (4H, m), 4.15-4.4 (1H, m),4.45-5.2 (1H, m), 6.64 (1H, d, J=7.4 Hz), 6.9-7.7 (12H, m)

EXAMPLE 913

To a solution of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in acetic acid (10 ml) is added dropwise2,5-dimethoxytetrahydrofuran (0.19 ml), and the mixture is refluxed for1 hour. The reaction solution is concentrated and the resulting residueis purified by silica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized from ethylacetate/n-hexane to give5-(1-pyrrolyl)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.31 g) as colorless prisms, m.p. 208°-210° C.

EXAMPLE 914

To a solution of5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(2.5 g) in dichloromethane (30 ml) is added triethylamine (0.96 ml) andfurther thereto is added dropwise chloroacetyl chloride (0.55 ml) underice-cooling. The mixture is stirred for 5 minutes. The reaction solutionis concentrated and to the resulting residue is added water. Theprecipitated crystal is collected by filtration, washed with water, anddried to give5-(2-chloroacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.4 g) as white powder.

¹ H-NMR (DMSO-d₆) δ; 1.3-2.15 (4H, m), 2.32 (3H, s), 2.8-3.05 (1H, m),4.24 (2H, AB-q, J=12.8, 15.4 Hz), 4.35-4.55 (1H, m), 4.9-5.25 (1H, m),6.68 (1H, d, J=7.6 Hz), 6.9-7.45 (9H, m), 7.52 (2H, d, J=8.6 Hz),8.9-9.05 (1H, m), 10.31 (1H, s)

Using the suitable starting materials, the compound of above Example 814is obtained in the same manner as in above Example 914.

EXAMPLE 915

A mixed solution of5-(2-chloroacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g), imidazole (0.1 g) and potassium carbonate (0.19 g) inacetonitrile (30 ml) is refluxed for 8 hours. The reaction solution isconcentrated and the resulting residue is washed with water andseparated by decantation. The remainder is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=20:1→15:1), andrecrystallized from ethanol/n-hexane to give5-[2-(1-imidazolyl)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.15 g) as colorless needles, m.p. 250°-252° C.

Using the suitable starting materials, the compound of above Example 818is obtained in the same manner as in above Example 915.

EXAMPLE 916

To a solution of5-(2-chloroacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g) in dimethylformamide (20 ml) are added dimethylaminehydrochloride (0.21 g) and potassium carbonate (0.54 g), and the mixtureis stirred at room temperature for 2 days. The reaction solution isconcentrated and water is added to the resulting residue. Theprecipitated crystal is collected by filtration, and recrystallized fromethyl acetate to give5-(2-dimethylaminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.24 g) as colorless prisms, m.p. 214°-216° C.

Using the suitable starting materials, the compounds of above Examples816, 817, 820, 821, 826 and 827 are obtained in the same manner as aboveExample 916.

EXAMPLE 917

A mixture of5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.6 g), N,N-dimethyl-2-chloroacetamide (0.19 g) and potassium carbonate(0.22 g) is refluxed for 24 hours. The reaction solution is concentratedand water is added to the resulting residue. The mixture is extractedthree times with dichloromethane. The extract is washed with saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is purified by silica gel columnchromatography (eluent; dichloromethane:methanol=30:1) to give5-[N-methyl-N-(dimethylaminocarbonylmethyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.05 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.2-3.3 (17H, m), 3.45 (2B, AB-q, J=14.7, 22.9 Hz),3.9-4.35 (2H, m), 6.60 (1H, d, J=7.7 Hz), 6.8-8.0 (11H, m), 8.39 (1H, s)

EXAMPLE 918

To a solution of t-butoxycarbonylglycine (0.84 g) in dimethylformamide(20 ml) are added diethyl cyanophosphate (0.73 ml) and5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.74 g), and further thereto is added triethylamine (1.8 ml) underice-cooling. The mixture is stirred for 30 minutes, and then stirred atroom temperature overnight. The reaction solution is concentrated andwater is added to the resulting residue. The precipitated crystal iscollected by filtration, washed with water, and recrystallized fromethyl acetate to give5-(2-aminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(E) (0.16 g). Separately, the liltrate is concentrated and purified bysilica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized from diethyl ether togive5-[2-(t-butoxycarbonylamino)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(F) (0.19 g).

(E):Colorless prisms, m.p. 287°-289° C.

(F):Colorless prisms, m.p. 170°-171° C.

EXAMPLE 919

5-Oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) is suspended in tetrahydrofuran (20 ml), and thereto is addeddropwise a 3.0M solution of methyl magnesium bromide in diethyl ether(1.5 ml) at room temperature. The mixture is stirred at room temperaturefor 1 hour. The reaction solution is poured into ice-water (20 ml), andextracted with ethyl acetate. The extract is dried over magnesiumsulfate, and the solvent is distilled off. The resulting residue ispurified by silica gel column chromatography (eluent; ethylacetate:n-hexane=2:3→1:1), and recrystallized from ethylacetate/n-hexane to give5-methyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.23 g) as white powder, m.p. 204°-205° C.

EXAMPLE 920

To a solution of5-carboxymethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.50 g) in dimethylformamide (60 ml) are added successivelythiomorpholine (0.66 ml), diethyl cyanophosphate (0.89 g) andtriethylamine (1.37 ml) with stirring under ice-cooling. The mixture isstirred for 30 minutes under ice-cooling, and at room temperature for 20minutes. Water (60 ml) is added to the reaction solution, and extractedwith dichloromethane. The extract is dried over magnesium sulfate, andthe solvent is distilled off. The resulting residue is purified bysilica gel column chromatography (eluent; ethylacetate:n-hexane=5:2→3:1), and recrystallized from ethylacetate/n-hexane to give5-(thiomorpholinocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1.60 g) as white powder, m.p. 235°-237° C.

Using the suitable starting materials, the compounds of above Examples829-838 are obtained in the same manner as in above Example 920.

EXAMPLE 921

To a solution of5-(thiomorpholinocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.40 g) in dichloromethane (40 ml) is added 80% m-chloroperbenzoic acid(175 mg) with stirring at -8° C., and the mixture is stirred at -8° C.for 1 hour. To the reaction solution is added 20% aqueous sodiumhydrogensulfite solution (40 ml) and the mixture is stirred at roomtemperature for 30 minutes. The dichloromethane layer is collected,washed with saturated saline solution and dried over magnesium sulfate.The solvent is distilled off and the resulting residue is purified bysilica gel column chromatography (eluent; dichlpromethane:methanol=20:1)to give5-[(1-oxothiomorpholino)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.32 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.50-1.92 (3H, m), 1.92-2.05 (1H, m), 2.47 (3H, s),2.55-3.06 (5H, m), 3.43-5.76 (8H, m), 6.63-6.82 (1H, m), 6.97-8.08 (12H,m)

EXAMPLE 922

To a solution of5-(thiomorpholinocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.40 g) in dichloromethane (40 ml) is added 80% m-chloroperbenzoic acid(0.35 g), and the mixture is stirred at room temperature for 1 hour. Thereaction solution is washed successively with an aqueous sodiumhydrogensulfite solution and saturated saline solution, and dried overmagnesium sulfate. The solvent is distilled off to give5-[(1,1-dioxothiomorpholino)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.41 g) as colorless amorphous.

¹ H-NMR (CDCl₃) δ; 1.43-2.65 (4H, m), 2,48 (3H, s), 2.69-3.25 (5H, m),3.90-5.40 (8H, m), 6.64-6.94 (1H, m), 6.94-7.77 (12H, m)

EXAMPLE 923

To a solution of5-oxo-1-[4-(2-hydroxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(400 mg) in acetone (20 ml) are added potassium carbonate (210 mg),potassium iodide (250 mg) and 2-chloroacetamide (120 mg), and themixture is refluxed for 2 hours. The insoluble materials are removed byfiltration, and the filtrate is distilled off. Dichloromethane is addedto the resulting residue, and the mixture is washed with saturatedsaline solution, and dried over magnesium sulfate. The solvent isdistilled off and the resulting residue is recrystallized from ethylacetate/n-hexane to give5-oxo-1-[4-(2-carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(436 mg) as white powder, m.p. 226°-228° C.

Using the suitable starting materials, the compound of above Example 842is obtained in the same manner as above Example 923.

EXAMPLE 924

A mixture of5-methylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.13 g), ethyl α-bromoacetate (58 mg), diisopropylethylamine (49 mg)and acetonitrile (5 ml) is refluxed for 10 hours. Acetonitrile isdistilled off under reduced pressure, and the resulting residue isdissolved in dichloromethane, washed with water, dried over magnesiumsulfate, and distilled off under reduced pressure. The resulting residueis purified by silica gel column chromatography (eluent;dichloromethane:methanol=50:1), and recrystallized fromchloroform/methanol to give7-[4-(2-chlorobenzoylamino)benzoyl]-1-methyl-1,2,3,4a,5,6,7,11b-octahydro-3-oxo[1]benzazepino[4,5-b][1,4]oxazine(80 mg) as colorless prisms, m.p. 286°-290° C.

EXAMPLE 925

To a solution of5-oxo-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(1 g) in methanol (20 ml) and dichloromethane (20 ml) is addedhydroxylamine-O-sulfonic acid (0.28 g) with stirring at roomtemperature, and the mixture is stirred at the same temperature for 1hour. Subsequently, to the reaction solution is added with stirring anaqueous solution of patassium carbonate (0.34 g) in water (1 ml) at roomtemperature, and the mixture is stirred at the same temperature for 2hours. The precipitated crystal is removed by filtration, and thefiltrate is concentrated under reduced pressure. The resulting residueis purified by silica gel column chromatography to give potassium{1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}imino-O-sulfonate(0.4 g) as white powder.

¹ H-NMR (DMSO-d₆) δ; 1.40-1.75 (1H, m), 1.90-2.15 (1H, m), 2.33 (3H, s),2.50-2.80 (2H, m), 3.10-3.50 (1H, m), 4.40-4.65 (1H, m), 6.85-7.60 (10H,m), 7.85 (1H, s), 10.44 (1H, s)

EXAMPLE 926

Using the suitable starting materials, the compounds of above Examples841-843, 868-870, 888 and 889 are obtained in the same manner as inabove Example 380.

EXAMPLE 927

Using the suitable starting materials, the compounds of above Examples876-878 are obtained in the same manner as in above Example 381.

EXAMPLE 928

Using the suitable starting materials, the compounds of above Examples840, 842 and 846 are obtained in the same manner as in above Example384.

EXAMPLE 929

Using the suitable starting materials, the compounds of above Examples788-790, 796-804, 805, 808, 811, 814, 818, 819, 824, 826, 827, 837, 845,848, 850, 852, 855, 856-858, 860, 861, 863-882, 885, 886, 888-893 and895-898 are obtained in the same manner as in above Example 388.

EXAMPLE 930

Using the suitable starting materials, the compound of above Example 848is obtained in the same manner as in above Example 393.

EXAMPLE 931

Using the suitable starting materials, the compounds of above Examples841 and 842 are obtained in the same manner as in above Example 402.

EXAMPLE 932

Using the suitable starting materials, the compounds of above Examples882 and 897 are obtained in the same manner as in above Example 403.

EXAMPLE 933

Using the suitable starting materials, the compound of above Example 809is obtained in the same manner as in above Example 634.

EXAMPLE 934

Using the suitable starting materials, the compounds of above Examples828-838 are obtained in the same manner as in above Example 640.

EXAMPLE 935

Using the suitable starting materials, the compound of above Example 810is obtained in the same manner as in above Example 772.

EXAMPLE 936

Using the suitable starting materials, the compound of above Example 788is obtained in the same manner as in above Example 771.

EXAMPLE 937

Using the suitable starting materials, the compounds of above Examples785, 787, 788-790, 796-805, 806, 807, 808, 811, 814, 818, 819, 845, 848,849, 850, 852, 855, 856-858, 860, 861, 863-882, 885, 886, 888-893 and896-898 are obtained in the same manner as in above Example 390.

EXAMPLE 938

To5-methanesulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benozyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.50 g) is added a 30% solution of methylamine in methanol (50 ml), andthe mixture is heated at 100° C. for 3 hours in a sealed tube. Aftercooling, the reaction solution is evaporated under reduced pressure, andthe resulting residue is purified by silica gel column chromatography(eluent; dichloromethane:methanol:aqueous ammonia=100:10:1) to give5-methylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.07 g).

¹ H-NMR (DMSO-d₆) δ; 1.40-2.18 (4H, m), 2.34 (3H, s), 2.47 (3H, s),2.54-3.50 (4H, m), 4.30-5.08 (1H, m), 6.56-6.82 (1H, m), 6.87-7.48 (10H,m), 7.48-7.75 (2H, m), 10.35 (1H, s)

Using the suitable starting materials, the compounds of above Examples823-825 are obtained in the same manner as in above Example 938.

Using the above suitable starting materials, the compounds of thefollowing Table 6 are obtained in the same manner as in Examples 1 and382. ##STR896##

EXAMPLE 939 ##STR897## Crystalline form: White powder Recrystallizationsolvent: Ethanol Melting Point: 208°-211° C. Form: Free EXAMPLE 940##STR898##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 171.5°-172.5° C.

Form: Free

EXAMPLE 941 ##STR899##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 151°-154° C.

Form: Free

EXAMPLE 942 ##STR900##

Crystalline form: Colorless amorphous

NMR analysis: 167)

Form: Free

EXAMPLE 943 ##STR901##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 180°-183° C.

Form: Free

EXAMPLE 944 ##STR902##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 109°-110° C.

Form: Free

EXAMPLE 945 ##STR903##

Crystalline form: Colorless oil

NMR analysis: 168)

Form: Free

EXAMPLE 946 ##STR904##

Crystalline form: Colorless oil

NMR analysis: 169)

Form: Free

EXAMPLE 947 ##STR905##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 177°-178.5° C.

Form: Free

EXAMPLE 948 ##STR906##

Crystalline form: Colorless amorphous

NMR analysis: 170)

Form: Free

EXAMPLE 949 ##STR907##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 162°-165° C.

Form: Free

EXAMPLE 950 ##STR908##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 212°-215° C.

Form: Free

EXAMPLE 951 ##STR909##

Crystalline form: Colorless oil

NMR analysis: 171)

Form: Free

EXAMPLE 952 ##STR910##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 112°-114° C.

Form: Free

EXAMPLE 953 ##STR911##

Crystalline form: Colorless oil

NMR analysis: 172)

Form: Free

EXAMPLE 954 ##STR912##

Crystalline form: Colorless amorphous

NMR analysis: 173)

Form: Free

EXAMPLE 955 ##STR913##

Crystalline form: Light yellow amorphous

NMR analysis: 174)

Form: Free

EXAMPLE 956 ##STR914##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether

Melting Point: 189°-193° C.

Form: Free

EXAMPLE 957 ##STR915##

Crystalline form: Colorless amorphous

NMR analysis: 175)

Form: Free

EXAMPLE 958 ##STR916##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol

Melting Point: 234°-238° C.

Form: Free

EXAMPLE 959 ##STR917##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/dichloromethane

Melting Point: 183°-184.5° C.

Form: Free

EXAMPLE 960 ##STR918##

Crystalline form: Brown oil

NMR analysis: 176)

Form: Free

EXAMPLE 961 ##STR919##

Crystalline form: Colorless amorphous

NMR analysis: 177)

Form: Free

EXAMPLE 962 ##STR920##

Crystalline form: Colorless amorphous

NMR analysis: 178)

Form: Free

EXAMPLE 963 ##STR921##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 202.5°-204.5° C.

Form: Free

EXAMPLE 964 ##STR922##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 199.5°-201° C.

Form: Free

EXAMPLE 965 ##STR923##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 196.5°-197° C.

Form: Free

EXAMPLE 966 ##STR924##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 204°-205° C.

Form: Free

EXAMPLE 967 ##STR925##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 175°-177° C.

Form: Free

EXAMPLE 968 ##STR926##

Crystalline form: Pink amorphous

NMR analysis: 179)

Form: Free

EXAMPLE 969 ##STR927##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 186°-189° C.

Form: Free

EXAMPLE 970 ##STR928##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 211°-212° C.

Form: Free

EXAMPLE 971 ##STR929##

Crystalline form: Colorless amorphous

NMR analysis: 180)

Form: Free

EXAMPLE 972 ##STR930##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol

Melting Point: 206°-207° C.

Form: Free

EXAMPLE 973 ##STR931##

Crystalline form: Colorless amorphous

NMR analysis: 181)

Form: Free

EXAMPLE 974 ##STR932##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 152°-154° C.

Form: Free

EXAMPLE 975 ##STR933##

Crystalline form: Colorless amorphous

NMR analysis: 182)

Form: Free

EXAMPLE 976 ##STR934##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 204°-206° C.

Form: Free

EXAMPLE 977 ##STR935##

Crystalline form: Colorless needles

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 162°-163° C.

Form: Free

167) ¹ H-NMR (CDCl₃) δ; 1.14-2.83 (13H, m), 2.43 (3H, s), 2.95-5.19 (4H,m), 4.12 (2H, t, J=6.2 Hz), 6.27-6.83 (2H, m), 6.83-7.36 (6H, m),7.36-7.67 (4H, m), 7.93-8.11 (1H, m), 9.77 (1H, brs)

168) ¹ H-NMR (CDCl₃) δ; 1.11-2.98 (11H, m), 2.80 (3H, s), 3.69 (2H, s),2.98-5.24 (2H, m), 6.50-7.71 (12H, m), 9.37 (1H, brs)

169) ¹ H-NMR (CDCl₃) δ; 1.10-2.80 (14H, m), 2.99 (3H, s), 3.39-5.20 (2H,m), 4.00 (2H, s), 6.49-7.67 (12H, m), 8.51 (1H, brs)

170) ¹ H-NMR (CDCl₃) δ; 1.10-1.98 (3H, m), 1.98-2.82 (10H, m), 2.82-3.20(2H, m), 3.34-5.15 (2H, m), 6.48-7.68 (15H, m), 7.86 (1H, brs)

171) ¹ H-NMR (CDCl₃) δ; 1.10-2.84 (10H, m), 2.40 (3H, s), 2.90-5.20 (2H,m), 3.79 (2H, d, J=2.7 Hz), 4.33 (1H, br), 6.30-7.68 (12H, m), 8.67 (1H,brs)

172) ¹ H-NMR (CDCl₃) δ; 1.10-2.85 (14H, m), 2.72 (3H, s), 2.98-5.20 (2H,m), 3.62 (2H, s), 6.50-7.75 (12H, m), 9.18 (1H, brs)

173) ¹ H-NMR (DMSO-d₆) δ; 1.28-2.62 (4H, m), 2.07 (3H, s), 2.34 (6H, s),3.04-3.57 (2H, m), 3.99-4.86 (1H, m), 6.62-7.88 (12H, m), 10.12-10.20(2H, m)

174) ¹ H-NMR (CDCl₃) δ; 1.39 (3H, t, J=7.1 Hz), 1.64-2.68 (4H, m), 2.42(6H, s), 3.04-3.58 (2H, m), 3.98-5.01 (1H, m), 4.38 (2H, q, J=7.1 Hz),6.57-8.57 (13H, m)

175) ¹ H-NMR (DMSO-d₆) δ; 1.67-5.02 (7H, m), 3.35 (6H, s), 6.75-8.17(12H, m), 8.46 (1H, s), 10.54 (1H, s)

176) ¹ H-NMR (CDCl₃) δ; 1.21 (3H, t, J=7.1 Hz), 1.95-2.30 (2H, m), 2.88(2H, t, J=6.2 Hz), 3.40-3.65 (2H, m), 3.70-4.50 (2H, m), 3.91 (2H, s),6.66 (1H, d, J=8.5 Hz), 6.70-7.00 (3H, m), 7.10-7.50 (7H, m), 7.81 (1H,d, J=2.5 Hz), 8.44 (1H, s)

177) ¹ H-NMR (CDCl₃) δ; 1.21 (3H, t, J=7 Hz), 1.30-5.20 (11H, m), 3.48(2H, q, J=7 Hz), 3.90 (2H, s), 6.53 (1H, d, J=8.3 Hz), 6.65-7.00 (4H,m), 7.00-7.40 (6H, m), 7.51 (1H, d, J=2.5 Hz), 8.40 (1H, s)

178) ¹ H-NMR (CDCl₃) δ; 1.21 (3H, t, J=7 Hz), 1.20-5.20 (15H, m), 3.90(2H, s), 6.48 (1H, d, J=8.3 Hz), 6.50-7.70 (11H, m), 8.39 (1H, s)

179) ¹ H-NMR (CDCl₃) δ; 1.60-2.20 (1H, m), 2.10-2.35 (1H, m), 2.45 (3H,s), 2.70-2.95 (2H, m), 3.25-3.45 (1H, m), 4.60-4.85 (1H, m), 7.10-7.80(12H, m)

180) ¹ H-NMR (CDCl₃) δ; 1.65-2.15 (4H, m), 2.46 (3H, s), 2.6-5.15 (4H,m), 6.75-6.95 (1H, m), 7.15-7.55 (10H, m), 7.61 (1H, s), 7.95-8.1 (1H,m)

181) ¹ H-NMR (CDCl₃) δ; 1.60-2.15 (3H, m), 2.15-2.90 (2H, m), 2.90-3.22(6H, m), 4.00-4.50 (2H, m), 4.13 (2H, s), 4.58-5.22 (2H, m), 6.53-6.80(1H, m), 6.90-7.90 (7H, m), 8.48 (1H, s)

182) ¹ H-NMR (CDCl₃) δ; 1.48-2.20 (3H, m), 2.20-2.85 (2H, m), 2.85-3.27(6H, m), 4.05-4.47 (2H, m), 4.47-5.22 (2H, m), 6.50-6.76 (1H, m),6.76-6.91 (1H, m), 6.91-7.69 (9H, m), 7.69-8.13 (1H, m), 9.28 (1H, s),11.87 (1H, brs)

EXAMPLE 978

5-Dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(H) (1.00 g) is dissolved in dichloromethane (30 ml), and thereto isadded triethylamine (0.48 ml) under ice-cooling, and further addeddropwise 2-methylbenzoyl chloride (0.44 ml). The mixture is stirred atroom temperature for 1 hour. The reaction solution is washed with water,and dried over magnesium sulfate. The solvent is distilled off, and theresulting residue is crystallized by adding thereto ethyl acetate. Theprecipitated crystal is recrystallized from dichloromethane/ethylacetate to give5-dimethylamino-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.92 g) as white powder, m.p. 191°-192° C.

HPLC retention time: 7.5 minutes

Column; Wakosil II 5C₁₈ (trade mark; Wako Pure Chemical Co., Ltd.)

Solvent; acetonitrile:50 mN aqueous Na₂ SO₄ solution:acetic acid=27:73:1

Rate; 1.0 ml/min.

[α]_(D) ²² =0° (c=1.0, chloroform)

¹ H-NMR (CDCl₃) δ; 1.15-3.25 (17H, m), 3.35-5.14 (2H, m), 6.62-8.05(12H, m)

Charts of ¹ H-NMR (CDCl₃) of the starting compound (H) and the compoundobtained in Exmaple 978 are shown in FIG. 1 and FIG. 2, respectively.

EXAMPLE 979

Using5-dimethylamino-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine(G) (1.00 g),5-dimethylamino-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(0.48 g) is obtained in the same manner as in Example 978 except thatmethanol/diethyl ether is used instead of ethyl acetate asrecrystallization solvent, as white powder, m.p. 183°-185° C.

HPLC retention time: 8.1 minutes (the conditions of HPLC are same asthose in Example 978)

[α]_(D) ²² =0° (c=1.3, chloroform)

¹ H-NMR (CDCl₃) δ; 1.10-3.20 (17H, m), 3.35-5.15 (2H, m), 6.50-6.80 (1H,m), 6.86-7.62 (10H, m), 7.65-8.09 (1H, m)

Charts of ¹ H-NMR (CDCl₃) of the starting compound (G) and the compoundobtained in Exmaple 979 are shown in FIG. 3 and FIG. 4, respectively.

REFERENCE EXAMPLE 18

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

7-Methoxy-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless needles, m.p. 178°-178.5° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 150°-151° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 116°-118° C. (recrystallized from ethylacetate/n-hexane)

7-Chloro-5-oxo-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder, m.p. 156°-158° C. (recrystallized from diethylether/dichloromethane)

REFERENCE EXAMPLE 19

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

7-Methoxy-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 172.5°-173.5° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder, m.p. 153°-155° C. (recrystallized from ethylacetate/n-hexane)

7-Methoxy-5-oxo-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless needles, m.p. 170°-171° C. (recrystallized from ethylacetate/n-hexane)

7-Chloro-5-oxo-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow oil

¹ H-NMR (CDCl₃) δ; 2.05-2.30 (2H, m), 2.85-3.00 (2H, m), 3.70 (3H, s),3.85-4.30 (4H, m), 6.42 (1H, d, J=8.1 Hz), 6.64 (1H, dd, J=1.7 Hz, 8.1Hz), 6.72 (1H, d, J=8.5 Hz), 6.80 (1H, d, J=1.8 Hz), 7.19 (1H, dd, J=2.6Hz, 8.5 Hz), 7.81 (1H, d, J=2.5 Hz)

Using the suitable starting materials, the compounds of the followingTable 7 are obtained in the same manner as in above Examples 1 and 382.##STR936##

EXAMPLE 980 ##STR937##

Crystalline form: Colorless amorphous

NMR analysis: 183)

Form: Free

EXAMPLE 981 ##STR938##

Crystalline form: Colorless amorphous

NMR analysis: 184)

Form: Free

EXAMPLE 982 ##STR939##

Crystalline form: Colorless amorphous

NMR analysis: 185)

Form: Free

EXAMPLE 983 ##STR940##

Crystalline form: Colorless amorphous

NMR analysis: 186)

Form: Free

EXAMPLE 984 ##STR941##

Crystalline form: Colorless amorphous

NMR analysis: 187)

Form: Free

EXAMPLE 985 ##STR942##

Crystalline form: Colorless amorphous

NMR analysis: 188)

Form: Free

EXAMPLE 986 ##STR943##

Crystalline form: Colorless amorphous

NMR analysis: 189)

Form: Free

EXAMPLE 987 ##STR944##

Crystalline form: White powder

Recrystallization solvent: Ethanol/water

Melting Point: 267°-268° C.

Form: Free

EXAMPLE 988 ##STR945##

Crystalline form: White powder

Recrystallization solvent: Ethanol/water

Melting Point: 264°-266° C.

Form: Free

EXAMPLE 989 ##STR946##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 218°-220° C.

Form: Free

EXAMPLE 990 ##STR947##

Crystalline form: Yellow oil

NMR analysis: 190)

Form: Free

EXAMPLE 991 ##STR948##

Crystalline form: Yellow oil

NMR analysis: 191)

Form: Free

EXAMPLE 992 ##STR949##

Crystalline form: Yellow powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 174°-177° C.

Form: Free

EXAMPLE 993 ##STR950##

Crystalline form: Yellow amorphous

NMR analysis: 192)

Form: Free

EXAMPLE 994 ##STR951##

Crystalline form: Colorless amorphous

NMR analysis: 193)

Form: Free

EXAMPLE 995 ##STR952##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/dichloromethane

Melting Point: 163°-165° C.

Form: Free

EXAMPLE 996 ##STR953##

Crystalline form: Colorless amorphous

NMR analysis: 194)

Form: Free

EXAMPLE 997 ##STR954##

Crystalline form: Colorless amorphous

NMR analysis: 195)

Form: Free

183) ¹ H-NMR (CDCl₃) δ; 1.10-2.83 (11H, m), 2.96-5.21 (2H, m), 4.55 (2H,s), 6.48-7.72 (13H, m), 8.30 (1H, brs)

184) ¹ H-NMR (CDCl₃) δ; 1.10-2.85 (11H, m), 1.58 (3H, d, J=6.8 Hz), 2.23(3H, s), 2.95-5.19 (4H, m), 6.38-7.70 (12H, m), 8.69 (1H, brs)

185) ¹ H-NMR (CDCl₃) δ; 1.10-2.85 (14H, m), 2.26 (3H, s), 2.96-5.19 (4H,m), 6.36-7.68 (12H, m), 8.72 (1H, brs)

186) ¹ H-NMR (CDCl₃) δ; 1.09-2.72 (11H, m), 1.53 (3H, d, J=6.9 Hz), 2.24(3H, s), 2.93-5.21 (4H, m), 6.30-7.78 (12H, m), 8.76 (1H, brs)

187) ¹ H-NMR (CDCl₃) δ; 1.10-2.82 (14H, m), 2.96-5.20 (4H, m), 6.38-7.70(12H, m), 8.54 (1H, brs)

188) ¹ H-NMR (CDCl₃) δ; 1.64-2.28 (2H, m), 2.41 (3H, s), 2.60-2.90 (2H,m), 2.90-3.70 (1H, m), 3.76 (3H, s), 4.10-5.10 (1H, m), 6.60-7.70 (10H,m), 8.51 (1H, s)

189) ¹ H-NMR (CDCl₃) δ; 1.64-2.43 (2H, m), 2.67-2.97 (2H, m), 3.00-3.70(1H, m), 3.77 (3H, s), 4.20-5.10 (1H, m), 6.60-7.75 (10H, m), 8.51 (1H,s)

190) ¹ H-NMR (CDCl₃) δ; 2.00-2.35 (2H, m), 2.49 (3H, s), 2.89 (2H, t,J=6.2 Hz), 3.72 (3H, s), 3.40-4.80 (2H, m), 6.74 (2H, d, J=8.5 Hz),6.80-7.00 (2H, m), 7.25-7.60 (5H, m), 7.80 (1H, d, J=2.6 Hz), 8.16 (1H,s), 8.37 (1H, d, J=8.6 Hz)

191) ¹ H-NMR (CDCl₃) δ; 1.90-2.40 (2H, m), 2.90 (2H, t, J=6.2 Hz), 3.75(3H, s), 3.40-4.80 (2H, m), 6.74 (1H, d, J=8.5 Hz), 6.80-7.00 (2H, m),7.10-7.50 (4H, m), 7.73 (1H, dd, J=2.3 Hz, 6 Hz), 7.80 (1H, d, J=2.5Hz), 8.38 (1H, d, J=8.8 Hz), 8.65 (1H, s)

192) ¹ H-NMR (CDCl₃) δ; 1.10-2.10 (13H, m), 2.90-5.20 (6H, m), 6.56 (1H,d, J=8.4 Hz), 6.69 (1H, d, J=7 Hz), 6.85-7.70 (7H, m), 8.15 (1H, s),8.31 (1H, d, J=8.4 Hz)

193) ¹ H-NMR (CDCl₃) δ; 0.30-0.65 (4H, m), 1.20-2.50 (7H, m), 2.50 (3H,s), 3.10-5.20 (2H, m), 3.75 (3H, s), 6.60 (1H, d, J=8.3 Hz), 6.70-7.60(8H, m), 8.14 (1H, s), 8.20-8.40 (1H, m)

194) ¹ H-NMR (CDCl₃) δ; 0.80-2.50 (10H, m), 2.90-4.10 (6H, m), 6.50-7.80(9H, m), 8.32 (1H, d, J=8 Hz), 8.62 (1H, s)

195) ¹ H-NMR (CDCl₃) δ; 0.30-0.65 (4H, m), 0.70-2.40 (6H, m), 2.60-5.20(6H, m), 6.50-7.80 (9H, m), 8.30 (1H, d, J=8 Hz), 8.62 (1H, s)

REFERENCE EXAMPLE 20

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

7-Methyl-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white needles

¹ H-NMR (CDCl₃) δ; 2.20 (2H, brs), 2.32 (3H, s), 2.88 (2H, t, J=6.3 Hz),3.40-4.79 (2H, m), 6.57 (1H, d, J=8.0 Hz), 7.04 (1H, d, J=7.7 Hz), 7.36(2H, d, J=8.6 Hz), 7.62 (1H, d, J=1.7 Hz), 8.04 (2H, d, J=8.7 Hz)

7-Dimethylamino-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,red brown prisms (recrystallized from dichloromethane/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.75-2.47 (2H, m), 2.60-3.62, 4.51-4.92 (total 4H,m), 2.93 (6H, s), 6.46 (1H, dd, J=2.2 Hz, 7.0 Hz), 6.52 (1H, d, J=7.0Hz), 7.33 (2H, d, J=7.0 Hz), 8.00 (2H, d, J=7.0 Hz)

7-Bromo-5-oxo-1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether), m.p.177°-182° C.

7-Chloro-5-oxo-1-(2-methyl-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.78-2.37 (2H, m), 2.48 (3H, s), 2.88 (2H, t, J=6.1Hz), 3.30-5.12 (2H, m), 6.47-6.82 (1H, m), 6.82-7.09 (1H, m), 7.09-7.27(1H, m), 7.48-8.35 (3H, m)

6-Oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.1 (4H, m), 2.85-4.7 (4H, m), 7.12 (1H, d, J=8.4Hz), 7.17-7.51 (4H, m), 7.89 (1H, dd, J=7.8 Hz, 2.1 Hz), 8.11 (1H, d,J=2.2 Hz)

8-Chloro-6-oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.15 (4H, m), 2.85-4.8 (4H, m), 7.14 (1H, d,J=8.5 Hz), 7.16 (1H, d, J=8.4 Hz), 7.34 (1H, dd, J=8.3 Hz, 2.5 Hz), 7.85(1H, d, J=2.5 Hz), 7.94 (1H, dd, J=8.4 Hz, 2.2 Hz), 8.13 (1H, d, J=2.1Hz)

8-Methyl-6-oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.65-2.2 (4H, m), 2.33 (3H, s), 2.7-5.0 (4H, m),7.0-7.25 (3H, m), 7.67 (1H, d, J=2.0 Hz), 7.89 (1H, dd, J=8.4 Hz, 2.2Hz), 8.10 (1H, d, J=2.1 Hz)

8-Methoxy-6-oxo-1-(2-chloro-4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.6-2.05 (4H, m), 2.8-5.2 (4H, m), 3.78 (3H, s), 6.88(1H, dd, J=8.6 Hz, 3.1 Hz), 7.11 (1H, d, J=8.4 Hz), 7.12 (1H, d, J=8.6Hz), 7.38 (1H, d, J=3.0 Hz), 7.90 (1H, dd, J=8.4 Hz, 2.2 Hz), 8.11 (1H,d, J=2.2 Hz)

7-Chloro-5-oxo-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder (recrystallized from diethyl ether/dichloromethane), m.p.125°-126.5° C.

REFERENCE EXAMPLE 21

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

7-Methyl-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder

¹ H-NMR (CDCl₃) δ; 2.13 (2H, brs), 2.32 (3H, s), 2.86 (2H, t, J=6.2 Hz),2.89-5.29 (2H, m), 3.86 (2H, brs), 6.41 (2H, m), 6.65 (1H, d, J=8.1 Hz),7.06 (3H, m), 7.65 (1H, d, J=1.7 Hz)

7-Dimethylamino-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow needles (recrystallized from dichloromethane/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.78-2.49 (2H, m), 2.64-3.78, 4.07-5.02 (total 4H,m), 2.93 (6H, m), 3.96 (2H, m), 6.38 (2H, d, J=8.7 Hz), 6.55 (1H, dd,J=2.7, 8.7 Hz), 6.62 (1H, d, J=8.7 Hz), 6.96-7.18 (3H, m)

7-Bromo-5-oxo-1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from methanol/diethyl ether)

¹ H-NMR (CDCl₃) δ; 1.98-2.37 (2H, m), 2.88 (2H, t, J=6.3 Hz), 3.52-4.55(4H, m), 6.28-6.57 (2H, m), 6.57-6.76 (1H, m), 6.92-7.20 (2H, m),7.28-7.42 (1H, m), 7.90-8.09 (1H, m)

7-Chloro-5-oxo-1-(2-methyl-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,white powder (recrystallized from dichloromethane/diethyl ether), m.p.190°-191° C.

6-Oxo-1-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.3-2.25 (4H, m), 2.8-4.4 (6H, m), 6.1-6.9 (3H, m),6.95-7.75 (3H, m), 7.8-8.3 (1H, m)

8-Chloro-6-oxo-1-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.59-2.2 (4H, m), 2.6-4.4 (6H, m), 6.1-6.9 (3H, m),6.95-7.5 (2H, m), 7.8-8.05 (1H, m)

7-Chloro-5-oxo-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder (recrystallized from diethyl ether/dichloromethane), m.p.188°-191.5° C.

Using the suitable starting materials, the compounds of the followingTable 8 are obtained in the same manner as in above Examples 1 and 382.##STR955##

EXAMPLE 998 ##STR956##

Crystalline form: White powder

NMR analysis: 196)

Form: Free

EXAMPLE 999 ##STR957##

Crystalline form: White powder

NMR analysis: 197)

Form: Free

EXAMPLE 1000 ##STR958##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 200°-205° C.

Form: Free

EXAMPLE 1001 ##STR959##

Crystalline form: Colorless amorphous

NMR analysis: 198)

Form: Free

EXAMPLE 1002 ##STR960##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 234°-238° C.

Form: Free

EXAMPLE 1003 ##STR961##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 174°-178° C.

Form: Free

EXAMPLE 1004 ##STR962##

Crystalline form: Light yellow amorphous

NMR analysis: 199)

Form: Free

EXAMPLE 1005 ##STR963##

Crystalline form: Light yellow amorphous

NMR analysis: 200)

Form: Free

EXAMPLE 1006 ##STR964##

Crystalline form: Light yellow amorphous

NMR analysis: 201)

Form: Free

EXAMPLE 1007 ##STR965##

Crystalline form: Light yellow amorphous

NMR analysis: 202)

Form: Free

EXAMPLE 1008 ##STR966##

Crystalline form: Light yellow amorphous

MNR analysis: 203)

Form: Free

EXAMPLE 1009 ##STR967##

Crystalline form: Light yellow amorphous

NMR analysis: 204)

Form: Free

EXAMPLE 1010 ##STR968##

Crystalline form: Colorless amorphous

NMR analysis: 205)

Form: Free

EXAMPLE 1011 ##STR969##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 153°-155° C.

Form: Free

EXAMPLE 1012 ##STR970##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 142°-143° C.

Form: Free

EXAMPLE 1013 ##STR971##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 176°-178° C.

Form: Free

EXAMPLE 1014 ##STR972##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 186°-188° C.

Form: Free

EXAMPLE 1015 ##STR973##

Crystalline form: Colorless amorphous

NMR analysis: 206)

Form: Free

EXAMPLE 1016 ##STR974##

Crystalline form: Colorless amorphous

NMR analysis: 207)

Form: Free

EXAMPLE 1017 ##STR975##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 191°-191.5° C.

Form: Free

EXAMPLE 1018 ##STR976##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 210°-212° C.

Form: Free

EXAMPLE 1019 ##STR977##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 196°-198° C.

Form: Free

EXAMPLE 1020 ##STR978##

Crystalline form: Colorless amorphous

NMR analysis: 208)

Form: Free

EXAMPLE 1021 ##STR979##

Crystalline form: Colorless amorphous

NMR analysis: 209)

Form: Free

EXAMPLE 1022 ##STR980##

Crystalline form: Colorless amorphous

NMR analysis: 210)

Form: Free

EXAMPLE 1023 ##STR981##

Crystalline form: Colorless amorphous

NMR analysis: 211)

Form: Free

EXAMPLE 1024 ##STR982##

Crystalline form: Colorless amorphous

NMR analysis: 212)

Form: Free

EXAMPLE 1025 ##STR983##

Crystalline form: Colorless amorphous

NMR analysis: 213)

Form: Free

EXAMPLE 1026 ##STR984##

Crystalline form: Colorless amorphous

NMR analysis: 214)

Form: Free

EXAMPLE 1027 ##STR985##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol

Melting Point: 207°-208° C.

Form: Free

EXAMPLE 1028 ##STR986##

Crystalline form: White powder

Recrystallization solvent: Ethanol

Melting Point: 201°-202° C.

Form: Free

EXAMPLE 1029 ##STR987##

Crystalline form: White powder

Recrystallization solvent: Ethanol

Melting Point: 193°-194° C.

Form: Free

EXAMPLE 1030 ##STR988##

Crystalline form: White powder

Recrystallization solvent: Ethanol

Melting Point: 205°-208° C.

Form: Free

EXAMPLE 1031 ##STR989##

Crystalline form: White powder

Recrystallization solvent: Ethanol

Melting Point: 214°-216° C.

Form: Free

EXAMPLE 1032 ##STR990##

Crystalline form: Yellow needles

Recrystallization solvent: Ethanol

Melting Point: 223°-226° C.

Form: Free

EXAMPLE 1033 ##STR991##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol/diethyl ether

Melting Point: 203°-206° C.

Form: Free

EXAMPLE 1034 ##STR992##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol/diethyl ether/n-hexane

Melting Point: 168°-171° C.

Form: Free

EXAMPLE 1035 ##STR993##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 206°-208° C.

Form: Free

EXAMPLE 1036 ##STR994##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 229°-232° C.

Form: Free

EXAMPLE 1037 ##STR995##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 220°-222° C.

Form: Free

EXAMPLE 1038 ##STR996##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 232°-233.5° C.

Form: Free

EXAMPLE 1039 ##STR997##

Crystalline form: Colorless amorphous

NMR analysis: 215)

Form: Free

EXAMPLE 1040 ##STR998##

Crystalline form: Colorless amorphous

NMR analysis: 216)

Form: Free

EXAMPLE 1041 ##STR999##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 147°-151° C.

Form: Free

EXAMPLE 1042 ##STR1000##

Crystalline form: White powder

Recrystallization solvent: Methanol/n-hexane

Melting Point: 127°-129° C.

Form: Free

EXAMPLE 1043 ##STR1001##

Crystalline form: White powder

Recrystallization solvent: Methanol/n-hexane

Melting Point: 109°-112° C.

Form: Free

EXAMPLE 1044 ##STR1002##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 198°-200° C.

Form: Free

EXAMPLE 1045 ##STR1003##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 210°-211° C.

Form: Free

EXAMPLE 1046 ##STR1004##

Crystalline form: Colorless amorphous

NMR analysis: 217)

Form: Free

EXAMPLE 1047 ##STR1005##

Crystalline form: Colorless amorphous

NMR analysis: 218)

Form: Free

EXAMPLE 1048 ##STR1006##

Crystalline form: Colorless amorphous

NMR analysis: 219)

Form: Free

EXAMPLE 1049 ##STR1007##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol

Melting Point: 243°-243.5° C.

Form: Free

EXAMPLE 1050 ##STR1008##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol/petroleum ether

Melting Point: 207°-209° C.

Form: Free

EXAMPLE 1051 ##STR1009##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol/petroleum ether

Melting Point: 239°-241° C.

Form: Free

EXAMPLE 1052 ##STR1010##

Crystalline form: Colorless amorphous

NMR analysis: 220)

Form: Free

EXAMPLE 1053 ##STR1011##

Crystalline form: Colorless amorphous

NMR analysis: 221)

Form: Free

EXAMPLE 1054 ##STR1012##

Crystalline form: Light yellow amorphous

NMR analysis: 222)

Form: Free

EXAMPLE 1055 ##STR1013##

Crystalline form: Light yellow amorphous

NMR analysis: 223)

Form: Free

EXAMPLE 1056 ##STR1014##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/dichloromethane

Melting Point: 169.5°-173° C.

Form: Free

EXAMPLE 1057 ##STR1015##

Crystalline form: Colorless amorphous

NMR analysis: 224)

Form: Free

EXAMPLE 1058 ##STR1016##

Crystalline form: Colorless amorphous

NMR analysis: 225)

EXAMPLE 1059 ##STR1017##

Crystalline form: Colorless amorphous

NMR analysis: 226)

Form: Free

EXAMPLE 1060 ##STR1018##

Crystalline form: Colorless amorphous

NMR analysis: 227)

Form: Free

EXAMPLE 1061 ##STR1019##

Crystalline form: Colorless amorphous

NMR analysis: 228)

Form: Free

EXAMPLE 1062 ##STR1020##

Crystalline form: Colorless amorphous

NMR analysis: 229)

Form: Free

EXAMPLE 1063 ##STR1021##

Crystalline form: Colorless amorphous

NMR analysis: 230)

Form: Free

EXAMPLE 1064 ##STR1022##

Crystalline form: Colorless amorphous

NMR analysis: 231)

Form: Free

EXAMPLE 1065 ##STR1023##

Crystalline form: Colorless amorphous

NMR analysis: 232)

Form: Free

EXAMPLE 1066 ##STR1024##

Crystalline form: Colorless amorphous

NMR analysis: 233)

Form: Free

EXAMPLE 1067 ##STR1025##

Crystalline form: Colorless amorphous

NMR analysis: 234)

Form: Free

EXAMPLE 1068 ##STR1026##

Crystalline form: Colorless amorphous

NMR analysis: 235)

Form: Free

EXAMPLE 1069 ##STR1027##

Crystalline form: Colorless amorphous

NMR analysis: 236)

Form: Free

EXAMPLE 1070 ##STR1028##

Crystalline form: Colorless amorphous

NMR analysis: 237)

Form: Free

196) ¹ H-NMR (CDCl₃) δ; 2.14 (2H, brs), 2.33 (3H, s), 2.46 (3H, s), 2.85(2H, t, J=6.1 Hz), 4.83 (2H, brs), 6.64 (1H, d, J=8.1 Hz), 7.07 (1H, d,J=8.0 Hz), 7.21-7.48 (8H, m), 7.65 (1H, m), 7.74 (1H, brs)

197) ¹ H-NMR (CDCl₃) δ; 2.12 (2H, brs), 2.33 (3H, s), 2.85 (2H, t, J=6.2Hz), 2.88-5.28 (2H, m), 6.63 (1H, d, J=8.1 Hz), 7.06 (1H, dd, J=1.7 Hz,8.1 Hz), 7.19-7.69 (9H, m), 8.26 (1H, brs)

198) ¹ H-NMR (CDCl₃) δ; 0.49 (4H, m), 1.25-5.13 (9H, m), 2.33 (3H, s),2.45 (3H, s), 6.53 (1H, m), 6.79 (1H, m), 7.07-7.42 (9H, m), 7.73 (1H,m)

199) ¹ H-NMR (CDCl₃) δ; 2.04 (2H, brs), 2.29 (3H, s), 2.82 (2H, t, J=5.9Hz), 2.85-5.29 (2H, m), 6.82-7.69 (10H, m), 8.31 (1H, brs)

200) ¹ H-NMR (CDCl₃) δ; 2.05 (2H, brs), 2.29 (3H, s), 2.44 (3H, s), 2.79(2H, t, J=5.5 Hz), 2.82-5.28 (2H, m), 6.82-8.12 (11H, m)

201) ¹ H-NMR (CDCl₃) δ; 1.40-4.85 (11H, m), 2.51 (3H, s), 6.78-7.63(10H, m), 8.64 (1H, brs)

202) ¹ H-NMR (CDCl₃) δ; 1.40-4.85 (11H, m), 2.45 (3H, s), 2.50 (3H, s),6.78-7.55 (10H, m), 8.10 (1H, brs)

203) ¹ H-NMR (CDCl₃) δ; 0.49 (4H, m), 1.25-4.85 (9H, m), 2.28 (3H, s),6.77-7.62 (10H, m), 8.64 (1H, brs)

204) ¹ H-NMR (CDCl₃) δ; 0.48 (4H, m), 1.26-4.85 (9H, m), 2.29 (3H, s),2.44 (3H, s), 6.78-7.58 (10H, m), 8.18 (1H, brs)

205) ¹ H-NMR (CDCl₃) δ; 1.14 (6H, d, J=6.3 Hz), 1.52-2.20 (7H, m),2.20-2.60 (1H, m), 2.64-3.66 (10H, m), 4.00-4.50 (4H, m), 4.50-5.23 (2H,m), 6.57-7.90 (11H, m), 8.10-8.30 (1H, m), 9.97 (1H, s)

206) ¹ H-NMR (CDCl₃) δ; 1.24-2.08 (4H, m), 2.08-2.26 (3H, m), 2.26-3.16(4H, m), 3.47-4.03 (4H, m), 4.18-4.92 (1H, m), 6.40-7.94 (10H, m),8.45-9.03 (1H, m)

207) ¹ H-NMR (CDCl₃) δ; 1.26-2.10 (4H, m), 2.10-2.28 (3H, m), 2.28-3.20(1H, m), 3.43-4.06 (4H, m), 4.20-4.93 (1H, m), 6.40-8.00 (10H, m),8.78-9.30 (1H, m)

208) ¹ H-NMR (CDCl₃) δ; 1.10-1.98 (4H, m), 1.98-3.10 (7H, m), 3.30-3.90(4H, m), 3.90-5.10 (1H, m), 6.45-8.25 (12H, m)

209) ¹ H-NMR (CDCl₃) δ; 1.06-1.94 (4H, m), 1.94-3.19 (10H, m), 3.19-3.90(4H, m), 3.90-5.10 (1H, m), 6.44-8.60 (11H, m)

210) ¹ H-NMR (CDCl₃) δ; 1.06-1.97 (4H, m), 1.97-3.20 (7H, m), 3.20-3.92(4H, m), 3.92-5.10 (1H, m), 6.44-8.55 (11H, m)

211) ¹ H-NMR (CDCl₃) δ; 1.07-1.98 (4H, m), 1.98-3.10 (10H, m), 3.37-5.20(8H, m), 6.44-6.86 (3H, m), 6.97-7.60 (6H, m), 8.13 (1H, s), 8.19-8.38(1H, m)

212) ¹ H-NMR (CDCl₃) δ; 1.08-1.99 (4H, m), 1.99-3.13 (7H, m), 3.33-5.14(8H, m), 6.40-6.90 (3H, m), 6.95-7.56 (5H, m), 7.63-7.87 (1H, m),8.17-8.37 (1H, m), 8.60 (1H, s)

213) ¹ H-NMR (CDCl₃) δ; 0.30-0.64 (4H, m), 0.70-3.42 (9H, m), 3.42-5.10(5H, m), 6.40-8.70 (11H, m)

214) ¹ H-NMR (CDCl₃) δ; 0.30-0.76 (4H, m), 0.80-3.43 (6H, m), 3.50-5.00(5H, m), 6.40-9.04 (11H, m)

215) ¹ H-NMR (CDCl₃) δ; 1.25-3.25 (14H, m), 3.55-5.06 (2H, m), 6.43-7.00(2H, m), 7.00-7.71 (8H, m), 7.91-8.45 (1H, m)

216) ¹ H-NMR (CDCl₃) δ; 1.11-3.20 (17H, m), 3.28-5.12 (2H, m), 6.41-7.01(2H, m), 7.02-7.63 (8H, m), 7.76-8.21 (1H, m)

217) ¹ H-NMR (CDCl₃) δ; 1.92-2.29 (2H, m), 2.36 (3H, s), 2.45 (3H, s),2.84 (2H, t, J=6.3 Hz), 3.32-4.64 (2H, m), 6.40-8.10 (11H, m)

218) ¹ H-NMR (CDCl₃) δ; 1.92-2.25 (2H, m), 2.34 (3H, s), 2.83 (2H, t,J=6.3 Hz), 3.21-4.52 (2H, m), 6.39-7.97 (10H, m), 8.43 (1H, brs)

219) ¹ H-NMR (CDCl₃) δ; 1.7-2.15 (4H, m), 2.5-5.2 (4H, m), 6.75-6.9 (1H,m), 7.27-7.6 (9H, m), 7.65-7.85 (1H, m), 7.9-8.15 (2H, m)

220) ¹ H-NMR (CDCl₃) δ; 1.65-2.1 (4H, m), 2.44 (3H, s), 2.8-4.5 (4H, m),6.75-8.0 (12H, m)

221) ¹ H-NMR (CDCl₃) δ; 1.65-2.3 (4H, m), 2.7-4.8 (4H, m), 6.75-8.4(12H, m)

222) ¹ H-NMR (CDCl₃) δ; 1.45-2.15 (4H, m), 2.45-2.55 (3H, m), 2.85-4.6(4H, m), 6.8-8.25 (11H, m)

223) ¹ H-NMR (CDCl₃) δ; 1.5-2.2 (4H, m), 2.8-4.7 (4H, m), 6.8-8.4 (11H,m)

224) ¹ H-NMR (CDCl₃) δ; 1.75-2.25 (2H, m), 2.30-2.70 (3H, m), 2.70-2.95(2H, m), 3.20-5.10 (2H, m), 6.70-8.40 (11H, m)

225) ¹ H-NMR (CDCl₃) δ; 1.20-2.60 (8H, m), 2.60-5.10 (3H, m), 6.80-7.90(10H, m), 8.20-8.60 (1H, m)

226) ¹ H-NMR (CDCl₃) δ; 1.20-2.60 (10H, m), 2.60-5.10 (3H, m), 6.80-8.15(11H, m)

227) ¹ H-NMR (CDCl₃) δ; 0.30-0.70 (4H, m), 1.20-2.45 (6H, m), 2.60-5.10(3H, m), 6.80-7.95 (10H, m), 8.15-8.50 (1H, m)

228) ¹ H-NMR (CDCl₃) δ; 1.20-2.40 (5H, m), 2.60-5.35 (7H, m), 5.80-6.15(1H, m), 6.75-7.95 (10H, m), 8.20-8.70 (1H, m)

229) ¹ H-NMR (CDCl₃) δ; 1.20-2.55 (7H, m), 2.60-5.35 (7H, m), 5.85-6.05(1H, m), 6.70-7.10 (2H, m), 7.10-7.90 (8H, m), 8.15-8.60 (1H, m)

230) ¹ H-NMR (CDCl₃) δ; 1.00-1.20 (6H, m), 1.00-2.40 (5H, m), 2.60-5.10(4H, m), 6.80-8.00 (10H, m), 8.15-8.65 (1H, m)

231) ¹ H-NMR (CDCl₃) δ; 0.80-2.50 (13H, m), 2.60-5.10 (4H, m), 6.70-8.85(10H, m), 8.25-8.60 (1H, m)

232) ¹ H-NMR (CDCl₃) δ; 1.30-2.60 (11H, m), 2.60-5.10 (3H, m), 6.80-8.15(11H, m)

233) ¹ H-NMR (CDCl₃) δ; 1.10-2.50 (13H, m), 2.50-5.10 (3H, m), 6.75-8.40(11H, m)

234) ¹ H-NMR (CDCl₃) δ; 0.30-0.65 (4H, m), 1.20-2.30 (6H, m), 2.35-2.55(3H, m), 2.60-5.10 (3H, m), 6.75-8.35 (11H, m)

235) ¹ H-NMR (CDCl₃) δ; 1.20-2.60 (8H, m), 2.60-5.40 (7H, m), 5.80-6.15(1H, m), 6.80-8.20 (11H, m)

236) ¹ H-NMR (CDCl₃) δ; 1.25-2.60 (10H, m), 2.60-5.40 (7H, m), 5.75-6.10(1H, m), 6.75-7.10 (2H, m), 7.10-8.40 (9H, m)

237) ¹ H-NMR (CDCl₃) δ; 0.95-1.20 (6H, m), 0.95-2.25 (5H, m), 2.40-2.60(3H, m), 2.60-5.10 (4H, m), 6.75-7.05 (2H, m), 7.10-8.30 (9H, m)

REFERENCE EXAMPLE 22

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 1.

8-Chloro-6-oxo-1-(4-nitrobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,yellow prisms

¹ H-NMR (DMSO-d₆) δ; 1.3-2.2 (4H, m), 2.6-5.0 (4H, m), 7.05-8.5 (7H, m)

5-Oxo-7-methyl-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.71-2.32 (2H, m), 2.29 (3H, s), 2.86 (2H, t, J=6.3Hz), 3.10-5.30 (2H, m), 6.84-8.38 (6H, m)

5-Oxo-7-methyl-1-(3-methoxy-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 2.17 (2H, brs), 2.34 (3H, s), 2.84 (2H, t, J=6.0 Hz),3.10-5.29 (2H, m), 3.77 (3H, s), 6.67 (1H, d, J=7.9 Hz), 6.85 (2H, m),7.10 (1H, d, J=8.0 Hz), 7.57-7.65 (2H, m)

5-Oxo-7-dimethylamino-1-(2-chloro-4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow powder

¹ H-NMR (CDCl₃) δ; 1.66-2.38 (2H, m), 2.65-2.88 (2H, m), 2.92 (6H, s),3.08-3.64, 4.58-5.01 (total 2H, m), 6.49 (1H, dd, J=3.1, 8.7 Hz), 6.82(1H, d, J=8.7 Hz), 6.90 (1H, d, J=3.1 Hz), 7.02-7.37 (1H, m), 7.94 (1H,dd, J=1.9, 8.4 Hz), 8.08 (1H, d, J=1.9 Hz)

REFERENCE EXAMPLE 23

Using the suitable starting materials, the following compounds areobtained in the same manner as in Reference Example 2.

8-Chloro-6-oxo-1-(4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.7-2.2 (4H, m), 2.3-4.8 (6H, m), 6.4-6.6 (2H, m),6.74 (1H, d, J=8.5 Hz), 7.1-7.4 (3H, m), 7.99 (1H, d, J=2.6 Hz)

8-Methyl-6-oxo-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,colorless amorphous

¹ H-NMR (CDCl₃) δ; 1.4-2.1 (4H, m), 2.15-2.6 (3H, m), 2.7-4.4 (6H, m),6.15-6.35 (1H, m), 6.51 (1H, s), 6.6-6.85 (1H, m), 6.9-7.25 (2H, m),7.72 (1H, s)

8-Methoxy-6-oxo-(2-chloro-4-aminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.4-2.2 (4H, m), 2.7-5.0 (9H, m), 6.25 (1H, dd, J=8.3Hz, 2.2 Hz), 6.51 (1H, d, J=2.2 Hz), 6.66 (1H, d, J=8.3 Hz), 6.88 (1H,dd, J=8.6 Hz, 3.0 Hz), 7.23 (1H, d, J=8.6 Hz), 7.43 (1H, d, J=3.0 Hz)

5-Oxo-7-chloro-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,colorless particles (recrystallized from methanol/diethyl ether), m.p.206°-208° C.

5-Oxo-7-methyl-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 2.09 (2H, brs), 2.29 (3H, s), 3.10-5.00 (2H, m), 3.78(2H, brs), 6.34-7.54 (6H, m)

5-Oxo-7-methyl-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,light yellow amorphous

¹ H-NMR (CDCl₃) δ; 2.12 (2H, brs), 2.32 (3H, s), 2.85 (2H, t, J=5.9 Hz),3.30-5.00 (2H, m), 3.65 (3H, s), 3.98 (2H, brs), 6.40 (1H, d, J=8.1 Hz),6.64-6.76 (3H, m), 7.06 (1H, dd, J=1.6, 8.1 Hz), 7.63 (1H, d, J=2.0 Hz)

5-Oxo-7-dimethylamino-1-(2-chloro-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine,yellow amorphous

¹ H-NMR (CDCl₃) δ; 1.60-2.32 (2H, m), 2.67-5.13 (4H, m), 2.92 (6H, s),3.75 (2H, s), 6.31 (1H, dd, J=2.1, 8.3 Hz), 6.46 (1H, d, J=2.1 Hz), 6.48(1H, dd, J=3.1, 8.7 Hz), 6.66-6.89 (2H, m), 6.95 (1H, d, J=3.1 Hz)

Using the stuitable starting materials, the compounds of the followingTable 9 are obtained in the same manner as in above Examples 1 and 382.##STR1029##

EXAMPLE 1071 ##STR1030##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol

Melting Point: 227°-230° C.

Form: Free

EXAMPLE 1072 ##STR1031##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol/petroleum ether

Melting Point: 216°-218° C.

Form: Free

EXAMPLE 1073 ##STR1032##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 227°-228° C.

Form: Free

EXAMPLE 1074 ##STR1033##

Crystalline form: White powder

NMR analysis: 238)

Form: Free

EXAMPLE 1075 ##STR1034##

Crystalline form: White powder

NMR analysis: 239)

Form: Free

EXAMPLE 1076 ##STR1035##

Crystalline form: Light yellow amorphous

NMR analysis: 240)

Form: Free

EXAMPLE 1077 ##STR1036##

Crystalline form: Light yellow amorphous

NMR analysis: 241)

Form: Free

EXAMPLE 1078 ##STR1037##

Crystalline form: Colorless amorphous

NMR analysis: 242)

Form: Free

EXAMPLE 1079 ##STR1038##

Crystalline form: Colorless amorphous

NMR analysis: 243)

Form: Free

EXAMPLE 1080 ##STR1039##

Crystalline form: Light yellow powder

Recrystallization solvent: Ethyl acetate/diethyl ether

Melting Point: 179°-181° C.

Form: Free

EXAMPLE 1081 ##STR1040##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/diethyl ether

Melting Point: 213°-216° C.

Form: Free

EXAMPLE 1082 ##STR1041##

Crystalline form: Light yellow powder

Recrystallization solvent: Ethyl acetate/diethyl ether

Melting Point: 185°-187° C.

Form: Free

EXAMPLE 1083 ##STR1042##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol

Melting Point: 249°-251° C.

Form: Free

EXAMPLE 1084 ##STR1043##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol

Melting Point: 239°-241° C.

Form: Free

EXAMPLE 1085 ##STR1044##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/diethyl ether

Melting Point: 208°-210° C.

Form: Free

EXAMPLE 1086 ##STR1045##

Crystalline form: White powder

Recrystallization solvent: Methanol/n-hexane

Melting Point: 178°-180.5° C.

Form: Free

EXAMPLE 1087 ##STR1046##

Crystalline form: Colorless amorphous

NMR analysis: 244)

Form: Free

EXAMPLE 1088 ##STR1047##

Crystalline form: Colorless amorphous

NMR analysis: 245)

Form: Free

EXAMPLE 1089 ##STR1048##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

NMR analysis: 246)

Form: Free

EXAMPLE 1090 ##STR1049##

Crystalline form: Colorless amorphous

NMR analysis: 247)

Form: Free

EXAMPLE 1091 ##STR1050##

Crystalline form: Colorless amorphous

NMR analysis: 248)

Form: Free

EXAMPLE 1092 ##STR1051##

Crystalline form: Colorless amorphous

NMR analysis: 249)

Form: Free

EXAMPLE 1093 ##STR1052##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 205°-206° C.

Form: Free

EXAMPLE 1094 ##STR1053##

Crystalline form: Colorless amorphous

NMR analysis: 250)

Form: Free

EXAMPLE 1095 ##STR1054##

Crystalline form: White powder

Recrystallization solvent: Methanol/n-hexane

Melting Point: 172.5°-174° C.

Form: Free

EXAMPLE 1096 ##STR1055##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 215°-216.5° C.

Form: Free

EXAMPLE 1097 ##STR1056##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 133°-136° C.

Form: Free

EXAMPLE 1098 ##STR1057##

Crystalline form: Colorless amorphous

NMR analysis: 251)

Form: Free

EXAMPLE 1099 ##STR1058##

Crystalline form: White powder

Recrystallization solvent: Methanol/n-hexane

Melting Point: 179°-180° C.

Form: Free

EXAMPLE 1100 ##STR1059##

Crystalline form: White powder

Recrystallization solvent: Methanol/n-hexane

Melting Point: 167.5°-169.5° C.

Form: Free

EXAMPLE 1101 ##STR1060##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 176°-178° C.

Form: Free

EXAMPLE 1102 ##STR1061##

Crystalline form: Colorless amorphous

NMR analysis: 252)

Form: Free

EXAMPLE 1103 ##STR1062##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 185°-188° C.

Form: Free

EXAMPLE 1104 ##STR1063##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 180°-181.5° C.

Form: Free

EXAMPLE 1105 ##STR1064##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 181°-184° C.

Form: Free

EXAMPLE 1106 ##STR1065##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 186.5°-187° C.

Form: Free

EXAMPLE 1107 ##STR1066##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 183°-184° C.

Form: Free

EXAMPLE 1108 ##STR1067##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 151°-153° C.

Form: Free

EXAMPLE 1109 ##STR1068##

Crystalline form: Colorless amorphous

NMR analysis: 253)

Form: Free

EXAMPLE 1110 ##STR1069##

Crystalline form: Colorless amorphous

NMR analysis: 254)

Form: Free

EXAMPLE 1111 ##STR1070##

Crystalline form: White needles

Recrystallization solvent: Ethanol/n-hexane

Melting Point: 191°-195° C.

Form: Free

EXAMPLE 1112 ##STR1071##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/n-hexane

Melting Point: 227°-230° C.

Form: Free

EXAMPLE 1113 ##STR1072##

Crystalline form: Colorless amorphous

NMR analysis: 289)

Form: Free

EXAMPLE 1114 ##STR1073##

Crystalline form: Light yellow amorphous

NMR analysis: 255)

EXAMPLE 1115 ##STR1074##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/n-hexane

Melting Point: 172°-174° C.

Form: Free

EXAMPLE 1116 ##STR1075##

Crystalline form: Colorless amorphous

NMR analysis: 305)

Form: Free

EXAMPLE 1117 ##STR1076##

Crystalline form: Colorless amorphous

NMR analysis: 290)

Form: Free

EXAMPLE 1118 ##STR1077##

Crystalline form: Colorless amorphous

NMR analysis: 291)

Form: Free

EXAMPLE 1119 ##STR1078##

Crystalline form: Colorless amorphous

NMR analysis: 264)

Form: Free

EXAMPLE 1120 ##STR1079##

Crystalline form: Colorless amorphous

NMR analysis: 265)

Form: Free

EXAMPLE 1121 ##STR1080##

Crystalline form: Colorless amorphous

NMR analysis: 266)

Form: Free

EXAMPLE 1122 ##STR1081##

Crystalline form: Colorless amorphous

NMR analysis: 267)

Form: Free

EXAMPLE 1123 ##STR1082##

Crystalline form: Colorless amorphous

NMR analysis: 268)

Form: Free

EXAMPLE 1124 ##STR1083##

Crystalline form: Colorless amorphous

NMR analysis: 269)

Form: Free

EXAMPLE 1125 ##STR1084##

Crystalline form: Colorless amorphous

NMR analysis: 270)

Form: Free

EXAMPLE 1126 ##STR1085##

Crystalline form: Colorless amorphous

NMR analysis: 271)

Form: Free

EXAMPLE 1127 ##STR1086##

Crystalline form: Colorless amorphous

NMR analysis: 272)

Form: Free

EXAMPLE 1128 ##STR1087##

Crystalline form: Colorless amorphous

NMR analysis: 273)

Form: Free

EXAMPLE 1129 ##STR1088##

Crystalline form: Colorless amorphous

NMR analysis: 274)

Form: Free

EXAMPLE 1130 ##STR1089##

Crystalline form: Colorless amorphous

NMR analysis: 275)

Form: Free

EXAMPLE 1131 ##STR1090##

Crystalline form: Colorless amorphous

NMR analysis: 276)

Form: Free

EXAMPLE 1132 ##STR1091##

Crystalline form: Colorless amorphous

NMR analysis: 277)

Form: Free

EXAMPLE 1133 ##STR1092##

Crystalline form: Colorless amorphous

NMR analysis: 278)

Form: Free

EXAMPLE 1134 ##STR1093##

Crystalline form: Colorless amorphous

NMR analysis: 279)

Form: Free

EXAMPLE 1135 ##STR1094##

NMR analysis: 280)

Form: Free

EXAMPLE 1136 ##STR1095##

NMR analysis: 281)

Form: Free

EXAMPLE 1137 ##STR1096##

NMR analysis: 282)

Form: Free

EXAMPLE 1138 ##STR1097##

NMR analysis: 283)

Form: Free

EXAMPLE 1139 ##STR1098##

NMR analysis: 306)

Form: Free

EXAMPLE 1140 ##STR1099##

Crystalline form: Colorless amorphous

NMR analysis: 284)

Form: Free

EXAMPLE 1141 ##STR1100##

Crystalline form: Colorless amorphous

NMR analysis: 285)

Form: Free

EXAMPLE 1142 ##STR1101##

Crystalline form: Colorless amorphous

NMR analysis: 286)

Form: Free

EXAMPLE 1143 ##STR1102##

Crystalline form: Colorless amorphous

NMR analysis: 287)

Form: Free

EXAMPLE 1144 ##STR1103##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 203°-207° C.

Form: Free

EXAMPLE 1145 ##STR1104##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 199°-203° C.

Form: Free

EXAMPLE 1146 ##STR1105##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 210°-212° C.

Form: Free

EXAMPLE 1147 ##STR1106##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 211°-214° C.

Form: Free

EXAMPLE 1148 ##STR1107##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 186°-189° C.

Form: Free

EXAMPLE 1149 ##STR1108##

Crystalline form: Colorless amorphous

NMR analysis: 288)

Form: Free

EXAMPLE 1150 ##STR1109##

Crystalline form: Colorless amorphous

NMR analysis: 292)

Form: Free

EXAMPLE 1151 ##STR1110##

Crystalline form: Colorless amorphous

NMR analysis: 293)

Form: Free

EXAMPLE 1152 ##STR1111##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 144°-145° C.

Form: Free

EXAMPLE 1153 ##STR1112##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 149°-150° C.

Form: Free

EXAMPLE 1154 ##STR1113##

Crystalline form: Colorless amorphous

NMR analysis: 294)

Form: Free

EXAMPLE 1155 ##STR1114##

Crystalline form: Colorless amorphous

NMR analysis: 295)

Form: Free

EXAMPLE 1156 ##STR1115##

Crystalline form: Colorless amorphous

NMR analysis: 301)

Form: Free

EXAMPLE 1157 ##STR1116##

Crystalline form: Colorless amorphous

NMR analysis: 302)

Form: Free

EXAMPLE 1158 ##STR1117##

Crystalline form: Colorless amorphous

NMR analysis: 303)

Form: Free

EXAMPLE 1159 ##STR1118##

Crystalline form: Colorless amorphous

NMR analysis: 304)

Form: Free

EXAMPLE 1160 ##STR1119##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/diisopropyl ether

Melting Point: 191°-193° C.

Form: Free

EXAMPLE 1161 ##STR1120##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/diisopropyl ether

Melting Point: 221°-223° C.

Form: Free

EXAMPLE 1162 ##STR1121##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 159°-161° C.

Form: Free

EXAMPLE 1163 ##STR1122##

Crystalline form: White powder

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 174°-175° C.

Form: Free

EXAMPLE 1164 ##STR1123##

Crystalline form: Colorless amorphous

NMR analysis: 256)

Form: Free

EXAMPLE 1165 ##STR1124##

Crystalline form: Colorless amorphous

NMR analysis: 257)

Form: Free

EXAMPLE 1166 ##STR1125##

Crystalline form: Colorless amorphous

NMR analysis: 258)

Form: Free

EXAMPLE 1167 ##STR1126##

Crystalline form: Colorless amorphous

NMR analysis: 259)

Form: Free

EXAMPLE 1168 ##STR1127##

Crystalline form: Colorless amorphous

NMR analysis: 260)

Form: Free

EXAMPLE 1169 ##STR1128##

Crystalline form: Colorless amorphous

NMR analysis: 261)

Form: Free

EXAMPLE 1170 ##STR1129##

Crystalline form: Colorless amorphous

NMR analysis: 296)

Form: Free

EXAMPLE 1171 ##STR1130##

Crystalline form: White powder

Recrystallization solvent: Ethanol/diethyl ether/n-hexane

Melting Point: 159°-162° C.

Form: Free

EXAMPLE 1172 ##STR1131##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol/diethyl ether/n-hexane

Melting Point: 221°-224° C.

Form: Free

EXAMPLE 1173 ##STR1132##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol/diethyl ether

Melting Point: 199°-202° C.

Form: Free

EXAMPLE 1174 ##STR1133##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol/diethyl ether

Melting Point: 215°-218° C.

Form: Free

EXAMPLE 1175 ##STR1134##

Crystalline form: Colorless needles

Recrystallization solvent: Ethanol/diethyl ether/n-hexane

Melting Point: 167°-170° C.

Form: Free

EXAMPLE 1176 ##STR1135##

Crystalline form: White powder

Recrystallization solvent: Ethanol/diethyl ether/n-hexane

Melting Point: 191°-193° C.

Form: Free

EXAMPLE 1177 ##STR1136##

Crystalline form: Light yellow amorphous

NMR analysis: 262)

Form: Free

EXAMPLE 1178 ##STR1137##

Crystalline form: Light yellow amorphous

NMR analysis: 263)

Form: Free

EXAMPLE 1179 ##STR1138##

Crystalline form: Colorless amorphous

NMR analysis: 297)

Form: Free

EXAMPLE 1180 ##STR1139##

Crystalline form: Colorless amorphous

NMR analysis: 298)

Form: Free

EXAMPLE 1181 ##STR1140##

Crystalline form: Colorless amorphous

NMR analysis: 299)

Form: Free

EXAMPLE 1182 ##STR1141##

Crystalline form: Colorless amorphous

NMR analysis: 300)

Form: Free

EXAMPLE 1183 ##STR1142##

Crystalline form: Colorless amorphous

NMR analysis: 307)

Form: Free

EXAMPLE 1184 ##STR1143##

Crystalline form: Colorless amorphous

NMR analysis: 308)

Form: Free

EXAMPLE 1185 ##STR1144##

Crystalline form: Colorless amorphous

NMR analysis: 309)

Form: Free

EXAMPLE 1186 ##STR1145##

Crystalline form: Colorless amorphous

NMR analysis: 310)

Form: Free

EXAMPLE 1187 ##STR1146##

Crystalline form: Colorless amorphous

NMR analysis: 311)

Form: Free

EXAMPLE 1188 ##STR1147##

Crystalline form: Colorless amorphous

NMR analysis: 312)

Form: Free

238) ¹ H-NMR (DMSO-d₆) δ; 1.4-2.1 (4H, m), 2.34 (3H, s), 2.8-5.4 (4H,m), 7.09 (1H, d, J=8.4 Hz), 7.15-7.7 (9H, m), 7.76 (1H, d, J=2.6 Hz),10.41 (1H, s)

239) ¹ H-NMR (DMSO-d₆) δ; 1.5-2.2 (4H, m), 2.8-5.2 (4H, m), 7.09 (1H, d,J=8.4 Hz), 7.2-7.7 (9H, m), 7.76 (1H, d, J=2.6 Hz), 10.63 (1H, s)

240) ¹ H-NMR (CDCl₃) δ; 1.65-2.2 (4H, m), 2.25-2.65 (6H, m), 2.75-4.6(4H, m), 6.8-8.15 (11H, m)

241) ¹ H-NMR (CDCl₃) δ; 1.4-2.25 (4H, m), 2.25-2.55 (3H, m), 2.7-4.8(4H, m), 6.8-8.3 (11H, m)

242) ¹ H-NMR (CDCl₃) δ; 1.4-2.1 (4H, m), 2.35-2.6 (3H, m), 2.8-5.2 (7H,m), 6.8-8.05 (11H, m)

243) ¹ H-NMR (CDCl₃) δ; 1.4-2.15 (4H, m) , 2.4-5.2 (7H, m), 6.8-7.85(10H, m), 7.9-8.3 (1H, m)

244) ¹ H-NMR (CDCl₃) δ; 1.20-2.38 (11H, m), 2.98-5.10 (3H, m), 6.45-7.04(2H, m), 7.05-7.86 (8H, m), 8.00-8.50 (1H, m)

245) ¹ H-NMR (CDCl₃) δ; 1.05-2.78 (14H, m), 2.78-5.18 (2H, m), 6.36-7.03(2H, m), 7.06-7.90 (8H, m), 7.98-8.39 (1H, m)

246) ¹ H-NMR (CDCl₃) δ; 1.75-2.54 (2H, m), 2.60-4.03 (4H, m), 3.37 (3H,brs), 5.17 (2H, s), 6.60-6.83 (3H, m), 6.90-7.07 (1H, m), 7.07-7.20 (1H,m), 7.22-7.50 (6H, m), 7.73-7.84 (1H, m)

247) ¹ H-NMR (CDCl₃) δ; 1.60-2.40 (2H, m), 2.45 (3H, s), 2.65-3.06 (2H,m), 3.06-5.28 (2H, m), 3.35 (3H, brs), 6.59-7.60 (9H, m), 7.67-7.88 (1H,m), 8.12 (1H, brs)

248) ¹ H-NMR (CDCl₃) δ; 1.60-2.52 (2H, m), 2.64-5.32 (4H, m ), 3.37 (3H,brs), 6.60-7.98 (10H, m), 8.50 (1H, b rs)

249) ¹ H-NMR (CDCl₃) δ; 1.18-3.15 (12H, m), 3.40-4.38 (5H, m ),6.58-7.75 (10H, m), 8.30-8.71 (1H, m)

250) ¹ H-NMR (CDCl₃) δ; 0.26-0.71 (4H, m), 1.15-3.29 (10H, m), 3.40-4.95(5H, m), 6.60-7.85 (10H, m), 8.18-8.68 (1H, m)

251) ¹ H-NMR (CDCl₃) δ; 0.25-0.72 (4H, m), 1.16-2.35 (6H, m), 2.35-3.30(4H, m), 3.43-4.98 (2H, m), 6.57-7.94 (10H, m), 8.22-8.89 (1H, m)

252) ¹ H-NMR (CDCl₃) δ; 0.69-2.90 (9H, m), 2.90-5.10 (5H, m), 6.40-7.85(10H, m), 8.25-8.54 (1H, m)

253) ¹ H-NMR (CDCl₃) δ; 2.17 (2H, brs), 2.34 (3H, s), 2.49 (3H, s), 2.87(2H, t, J=6.0 Hz), 3.10-5.00 (2H, m), 3.70 (3H, s), 6.67 (1H, d, J=8.0Hz), 6.85-6.88 (2H, m), 7.09 (1H, dd, J=1.5, 8.0 Hz), 7.21-7.50 (4H, m),7.64 (1H, d, J=1.9 Hz), 8.11 (1H, m), 8.33 (1H, d, J=8.8 Hz)

254) ¹ H-NMR (CDCl₃) δ; 1.42-5.06 (13H, m), 6.51 (1H, d, J=7.8 Hz), 6.76(1H, m), 7.01-7.63 (10H, m), 8.53 (1H, m)

255) ¹ H-NMR (CDCl₃) δ; 1.26-4.93 (16H, m), 6.69-7.73 (10H, m),8.62-8.84 (1H, m)

256) ¹ H-NMR (CDCl₃) δ; 1.45-1.90 (2H, m), 1.90-2.33 (2H, m), 2.33-3.25(4H, m), 3.60-3.93 (3H, m), 4.45-5.15 (2H, m), 6.40-8.25 (11H, m)

257) ¹ H-NMR (CDCl₃) δ; 1.49-1.97 (2H, m), 1.97-3.10 (3H, m), 3.58-3.98(3H, m), 4.60-5.26 (2H, m), 6.44-8.36 (11H, m)

258) ¹ H-NMR (CDCl₃) δ; 1.82-2.13 (1H, m), 2.13-2.43 (1H, m), 2.50 (3H,s), 2.57 (3H, s), 3.69-4.06 (3H, m), 3.78 (3H, s), 6.45-6.80 (2H, m),6.85-7.00 (1H, m), 7.18-7.80 (9H, m)

259) ¹ H-NMR (CDCl₃) δ; 1.72-2.05 (1H, m), 2.11-2.40 (1H, m), 2.51 (3H,s), 2.57 (3H, s), 3.40-4.20 (3H, m), 3.77 (3H, s), 6.35-6.64 (1H, m),6.79-6.96 (1H, m), 7.15-8.13 (9H, m)

260) ¹ H-NMR (CDCl₃) δ; 1.71-2.05 (1H, m), 2.07-2.32 (1H, m), 2.33 (6H,s), 2.47 (3H, s), 3.50-3.80 (2H, m), 3.76 (3H, s), 3.95-4.17 (1H, m),6.40-6.70 (2H, m), 6.90-7.03 (1H, m), 7.14-7.77 (8H, m), 7.90-8.14 (1H,m)

261) ¹ H-NMR (CDCl₃) δ; 1.76-2.70 (2H, m), 2.30 (6H, s), 2.47 (3H, s),3.23-4.40 (3H, m), 3.73 (3H, s), 6.30-6.65 (2H, m), 6.65-8.76 (9H, m)

262) ¹ H-NMR (CDCl₃) δ; 1.68-2.35 (2H, m), 2.36-5.11 [13H, m, 2.45 (3H,s), 2.92 (6H, s)], 6.56 (1H, dd, J=3.1, 8.7 Hz), 6.78-7.06 (2H, m), 6.82(1H, d, J=8.7 Hz), 7.11-7.68 (6H, m), 7.97 (1H, brs)

263) ¹ H-NMR (CDCl₃) δ; 1.69-2.30 (2H, m), 2.59-5.10 [10H, m, 2.92 (6H,s)], 6.56 (1H, dd, J=3.1, 8.8 Hz), 6.72-7.90 (9H, m), 8.42 (1H, brs)

264) ¹ H-NMR (CDCl₃) δ; 1.49 (1H, brs), 1.82-2.01 (1H, m), 2.03-2.26(1H, m), 2.46 (3H, s), 2.54 (3H, s), 3.67-3.76 (1H, m), 3.86 (2H, t,J=6.8 Hz), 6.67 (1H, d, J=8.6 Hz), 6.93 (1H, dd, J=8.6, 2.5 Hz),7.13-7.43 (9H, m), 8.15 (1H, brs)

265) ¹ H-NMR (CDCl₃) δ; 1.58 (1H, brs), 1.86-2.03 (1H, m), 2.08-2.30(1H, m), 2.56 (3H, s), 3.69-3.78 (1H, m), 3.91 (2H, t, J=6.5 Hz), 6.69(1H, d, J=8.7 Hz), 6.94 (1H, dd, J=8.6, 2.5 Hz), 7.33-7.47 (6H, m),7.54-7.63 (2H, m), 7.67-7.77 (1H, m), 8.16 (1H, brs)

266) ¹ H-NMR (CDCl₃) δ; 1.50 (1H, brs), 1.76-2.23 (2H, m), 2.42 (3H, s),2.47 (3H, s), 3.55-3.94 (3H, m), 6.28-7.78 (10H, m), 8.91 (1H, brs)

267) ¹ H-NMR (CDCl₃) δ; 1.46 (1H, brs), 1.82-2.28 (2H, m), 2.50 (3H, s),3.52-4.08 (3H, m), 6.34-7.75 (10H, m), 8.61 (1H, brs)

268) ¹ H-NMR (CDCl₃) δ; 1.80-2.31 (2H, m), 2.32 (3H, s), 2.48 (3H, s),3.51-3.82 (2H, m), 3.95-4.15 (1H, m), 6.59 (1H, d, J=8.6 Hz), 6.90 (1H,dd, J=8.6, 2.5 Hz), 7.16-7.61 (9H, m), 7.88 (1H, brs)

269) ¹ H-NMR (CDCl₃) δ; 1.86-2.04 (1H, m), 2.13-2.31 (1H, m), 2.33 (3H,s), 3.53-3.62 (1H, m), 3.76 (1H, dt, J=12.8, 6.4 Hz), 6.60 (1H, d, J=8.7Hz), 6.91 (1H, dd, J=8.7, 2.5 Hz), 7.33-7.52 (6H, m), 7.54-7.66 (2H, m),7.73-7.82 (1H, m), 8.07 (1H, brs)

270) ¹ H-NMR (CDCl₃) δ; 1.65-2.27 (2H, m), 2.28 (6H, s), 2.48 (3H, s),3.37-4.07 (3H, m), 6.33-7.91 (10H, m), 8.20 (1H, brs)

271) ¹ H-NMR (CDCl₃) δ; 1.71-2.26 (2H, m), 2.28 (6H, s), 3.36-4.10 (3H,m), 6.35-7.95 (10H, m), 8.59 (1H, brs)

272) ¹ H-NMR (CDCl₃) δ; 2.02-2.23 (2H, m), 2.28 (3H, s), 2.47 (3H, s),2.56 (3H, s), 3.73-4.07 (3H, m), 4.68 (1H, brs), 6.61 (1H, d, J=8.1 Hz),6.72-6.83 (1H, m), 7.17-7.63 (11H, m), 8.03 (1H, brs)

273) ¹ H-NMR (CDCl₃) δ; 1.61 (1H, brs), 1.87-2.25 (2H, m), 2.29 (3H, s),2.56 (3H, m), s), 3.67-3.78 (1H, m), 3.91 (2H, t, J=6.9 Hz), 6.52-6.79(2H, m), 7.09-7.15 (1H, m), 7.30-7.90 (8H, m), 8.23 (1H, brs)

274) ¹ H-NMR (CDCl₃) δ; 1.58 (1H, brs), 1.82-2.23 (2H, m), 2.27 (3H, s),2.48 (3H, s), 2.50 (3H, s), 3.47-4.05 (3H, m), 6.23-6.83 (2H, m),7.00-7.50 (7H, m), 7.53-7.74 (1H, m), 8.28 (1H, brs)

275) ¹ H-NMR (CDCl₃) δ; 1.60 (1H, brs), 1.82-2.35 (5H, m), 2.49 (3H, s),3.41-4.08 (3H, m), 6.30-6.80 (1H, m), 6.98-7.68 (8H, m), 7.31-7.82 (1H,m), 8.77 (1H, brs)

276) ¹ H-NMR (CDCl₃) δ; 1.76-2.03 (2H, m), 2.27 (3H, s), 2.32 (6H, s),2.47 (3H, s), 3.48-3.58 (1H, m), 3.66 (1H, dt, J=12.7, 6.1 Hz),3.97-4.14 (1H, m), 6.48 (1H, d, J=8.2 Hz), 6.65-6.77 (1H, m), 7.14-7.59(9H, m), 7.96 (1H, brs)

277) ¹ H-NMR (CDCl₃) δ; 1.75-2.04 (2H, m), 2.27 (3H, s), 2.33 (6H, s),3.48-3.58 (1H, m), 3.67 (1H, dt, J=12.7, 6.1 Hz), 3.98-4.16 (1H, m),6.48 (1H, d, J=8.2 Hz), 6.72 (1H, dd, J=8.2, 1.9 Hz), 7.16 (1H, d, J=1.9Hz), 7.27-7.91 (8H, m), 8.31 (1H, brs)

278) ¹ H-NMR (CDCl₃) δ; 1.72-2.05 (2H, m), 2.28 (9H, s), 2.47 (3H, s),3.16-4.34 (3H, m), 6.38-7.79 (10H, m), 8.37 (1H, brs)

279) ¹ H-NMR (CDCl₃) δ; 1.65-2.07 (2H, m), 2.28 (9H, s), 3.26-4.38 (3H,m), 6.34-8.06 (10H, m), 8.53 (1H, brs)

280) Two stereoisomers: Both colorless amorphous

Isomer A:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 1.04 (3H, d, J=6.9 Hz), 1.59 (1H, brs), 2.25-2.45(1H, m), 2.49 (3H, s), 2.52 (3H, s), 3.53-3.69 (2H, m), 3.91 (1H, abq,J=7.2, 12.9 Hz), 6.60 (1H, d, J=8.6 Hz), 6.93 (1H, dd, J=8.6, 2.5 Hz),7.18-7.60 (9H, m), 7.76 (1H, brs)

Isomer B:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 1.06 (3H, d, J=6.9 Hz), 1.60 (1H, brs), 2.21-2.43(1H, m), 2.47 (3H, s), 2.52 (3H, s), 3.51-3.66 (2H, m), 3.93 (1H, abq,J=7.5, 12.9 Hz), 6.60-6.68 (1H, m), 6.95 (1H, dt, J=7.5, 1.8 Hz), 7.03(1H, dt, J=7.4, 1.4 Hz), 7.17-7.55 (8H, m), 7.81 (1H, brs)

281) Two stereoisomers: Both colorless amorphous

Isomer A:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 1.04 (3H, d, J=6.9 Hz), 1.55 (1H, brs), 2.23-2.46(1H, m), 2.53 (3H, s), 3.53-3.67 (2H, m), 3.91 (1H, abq, J=7.1, 12.9Hz), 6.61 (1H, d, J=8.6 Hz), 6.93 (1H, dd, J=8.6, 2.5 Hz), 7.28-7.52(6H, m), 7.54-7.65 (2H, m), 7.70-7.79 (1H, m), 8.16 (1H, brs)

Isomer B:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 1.06 (3H, d, J=6.9 Hz), 1.61 (1H, brs), 2.21-2.42(1H, m), 2.51 (3H, s), 3.48-3.67 (2H, m), 3.90 (1H, abq, J=7.4, 12.9Hz), 6.59-6.67 (1H, m), 6.94 (1H, dt, J=7.5, 1.9 Hz), 7.03 (1H, dt,J=7.4, 1.4 Hz), 7.23-7.75 (8H, m), 8.41 (1H, brs)

282) Two stereoisomers: Both colorless amorphous

Isomer A:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 0.99 (3H, d, J=6.5 Hz), 1.37 (1H, brs), 2.16-2.40(1H, m), 2.46 (3H, s), 2.48 (3H, s), 3.38-3.96 (3H, m), 6.30-7.28 (10H,m), 8.26 (1H, brs)

Isomer B:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) 1.03 (3H, d, J=6.7 Hz), 1.44 (1H, brs), 2.17-2.40 (1H,m), 2.45 (3H, s), 2.47 (3H, s), 3.40-3.98 (3H, m), 6.47-7.73 (10H, m),8.23 (1H, brs)

283) Two stereoisomers: Both colorless amorphous

Isomer A:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 1.00 (3H, d, J=6.6 Hz), 1.40 (1H, brs), 2.18-2.42(1H, m), 2.47 (3H, s), 3.36-4.02 (3H, m), 6.32-7.78 (10H, m), 8.55 (1H,brs)

Isomer B:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 1.03 (3H, d, J=6.5 Hz), 1.39 (1H, brs), 2.14-2.39(1H, m), 2.45 (3H, s). 3.34-3.98 (3H, m), 6.53-7.98 (10H, m), 8.78 (1H,brs)

284) ¹ H-NMR (CDCl₃) δ; 1.05-1.25 (3H, m), 1.25-2.80 (10H, m), 3.00-5.10(3H, m), 6.75-8.40 (11H, m)

285) ¹ H-NMR (CDCl₃) δ; 1.00-2.80 (12H, m), 3.00-5.10 (3H, m), 6.70-7.80(10H, m), 8.30-8.80 (1H, m)

286) ¹ H-NMR (CDCl₃) δ; 0.95-2.80 (15H, m), 2.80-5.15 (3H, m), 6.70-7.05(2H, m), 7.10-7.80 (10H, m), 7.95-8.45 (1H, m)

287) ¹ H-NMR (CDCl₃) δ; 0.80-2.60 (16H, m), 2.60-5.05 (4H, m), 6.70-7.70(10H, m), 7.85-8.40 (1H, m)

288) ¹ H-NMR (CDCl₃) δ; 1.30-2.60 (8H, m), 2.60-5.10 (3H, m), 6.60-7.95(10H, m), 8.25-8.70 (1H, m)

289) ¹ H-NMR (CDCl₃) δ; 1.27-4.91 (19H, m), 6.68-7.73 (10H, m),8.40-8.71 (1H, m)

290) ¹ H-NMR (CDCl₃) δ; 1.81-2.54 (6H, m), 2.15 (3H, s), 2.41 (3H, s),2.46 (3H, s), 3.61-3.71 (3H, m), 6.91-7.43 (10H, m), 8.60 (1H, s)

291) ¹ H-NMR (CDCl₃) δ; 1.86-2.50 (3H, m), 2.28 (9H, s), 2.49 (3H, s),6.60-7.47 (10H, m), 7.75 (1H, m)

292) ¹ H-NMR (CDCl₃) δ; 1.15-2.55 (13H, m), 2.55-5.10 (3H, m), 6.60-8.40(11H, m)

293) ¹ H-NMR (CDCl₃) δ; 1.15-2.45 (10H, m), 2.55-5.10 (3H, m), 6.60-7.80(10H, m), 8.30-8.70 (1H, m)

294) ¹ H-NMR (CDCl₃) δ; 1.10-2.60 (4H, m), 2.41 (6H, s), 2.49 (3H, s),3.76 (3H, s), 2.60-5.20 (3H, m), 6.50-6.80 (3H, m), 6.90-7.60 (6H, m),8.13 (1H, s), 8.30 (1H, d, J=8.5 Hz)

295) ¹ H-NMR (CDCl₃) δ; 1.15-2.50 (4H, m), 2.41 (6H, s), 2.60-5.20 (3H,m), 3.77 (3H, s), 6.50-7.50 (8H, m), 7.65-7.80 (1H, m), 8.31 (1H, d,J=8.4 Hz), 8.61 (1H, s)

296) ¹ H-NMR (CDCl₃) δ; 1.55-3.13 (12H, m), 2.44 (3H, s), 4.60-5.14 (2H,m), 6.28 (1H, dd, J=2.5, 8.5 Hz), 6.48 (1H, d, J=8.5 Hz), 6.99 (1H, d,J=2.5 Hz), 7.07-7.58 (8H, m), 7.80 (1H, brs)

297) ¹ H-NMR (CDCl₃) δ; 1.01-2.88, 3.22-4.41, 4.90-5.28 [total 18H, 1.17(3H, t, J=7.2 Hz), 2.40 (3H, s), 3.77 (3H, s)], 6.55 (1H, d, J=8.1 Hz),6.60-7.98 (8H, m), 8.23-8.75 (2H, m)

298) ¹ H-NMR (CDCl₃) δ; 1.00-3.04, 3.24-4.45. 4.91-5.27 [total 21H, m,1.17 (3H, t, J=7.0 Hz), 2.39 (3H, s), 2.50 (3H, s), 3.75 (3H, s)], 8.56(1H, d, J=8.3 Hz), 6.69 (1H, d, J=8.3 Hz), 6.82-7.75 (7H, m), 8.05-8.49(2H, m)

299) ¹ H-NMR (CDCl₃) δ; 1.21-4.62, 4.90-5.43 (total 15H, m), 5.70-6.11(1H, m), 6.35-7.90 (9H, m), 8.07-8.92 (2H, m)

300) ¹ H-NMR (CDCl₃) δ; 1.20-4.68, 5.01-5.3 [total 18H, m, 2.50 (3H,s)], 5.72-6.14 (1H, m), 6.49-7.69 (9H, m), 8.01-8.58 (2H, m)

301) ¹ H-NMR (CDCl₃) δ; 1.25-2.80 (14H, m), 3.00-5.10 (6H, m), 6.40-8.00(11H, m)

302) ¹ H-NMR (CDCl₃) δ; 1.30-2.90 (11H, m), 3.00-5.10 (6H, m), 6.40-7.80(10H, m), 8.00-8.35 (1H, m)

303) ¹ H-NMR (CDCl₃) δ; 1.10-2.80 (16H, m), 2.85-5.15 (6H, m), 6.40-7.80(11H, m) `304) ¹ H-NMR (CDCl₃) δ; 1.10-2.80 (13H, m), 2.90-5.10 (6H, m),6.40-7.85 (10H, m), 7.90-8.20 (1H, m)

305) ¹ H-NMR (CDCl₃) δ; 1.27-5.28 (19H, m), 3.75 (3H, s), 6.51 (1H, d,J=7.9 Hz), 6.69-6.81 (2H, m), 7.05-7.49 (6H, m), 8.14 (1H, m), 8.27 (1H,d, J=8.4 Hz)

306) Two stereoisomers: Both colorless amorphous

Isomer A:

[α]_(D) ²² =0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 0.78-1.02 (3H, m), 2.23-2.52 (1H, m), 2.39 (6H, s),2.48 (3H, s), 3.17-4.30 (3H, m), 6.85-7.84 (10H, m), 8.17 (1H, brs)

Isomer B:

[α]_(D) ²² 0° (chloroform, c=1.0)

¹ H-NMR (CDCl₃) δ; 0.73-1.00 (3H, m), 2.17-2.52 (1H, m), 2.39 (6H, s),2.49 (3H, s), 3.15-4.33 (3H, m), 6.36-7.55 (8H, m), 7.58-7.83 (2H, m),8.19 (1H, brs)

307) ¹ H-NMR (CDCl₃) δ; 1.25-4.44, 4.98-5.41 [total 17H, m, 2.40 (3H,s), 3.76 (3H, s)], 5.72-6.13 (1H, m), 6.56 (1H, d, J=8.4 Hz), 6.69 (1H,d, J=7.9 Hz), 6.77-7.93 (7H, m), 8.32 (1H, d, J=8.3 Hz), 8.49-8.95 (1H,m)

308) ¹ H-NMR (CDCl₃) 1.23-5.42 (20H, m), 5.78-6.09 (1H, m), 6.56 (1H, d,J=8.3 Hz), 6.61-7.82 (8H, m), 8.14 (1H, s), 8.30 (1H, d, J=8 Hz)

309) ¹ H-NMR (CDCl₃) δ; 1.20-2.70 (11H, m), 2.80-4.90 (9H, m), 6.40-7.70(10H, m), 8.30-8.70 (1H, m)

310) ¹ H-NMR (CDCl₃) δ; 1.20-2.80 (8H, m), 2.85-5.05 (9H, m), 6.40-7.80(10H, m), 8.10-8.50 (1H, m)

311) ¹ H-NMR (CDCl₃) δ; 1.20-2.75 (13H, m), 2.80-5.10 (9H, m), 6.40-8.00(11H, m)

312) ¹ H-NMR (CDCl₃) δ; 1.20-2.80 (10H, m), 2.90-5.10 (9H, m), 6.40-7.80(10H, m), 8.00-8.40 (1H, m)

EXAMPLE 1189

By using di-p-toluoyl-L-tartaric acid monohydride ordi-p-toluoyl-D-tartaric acid monohydride, the compound obtained in aboveExample 408 is optically resovled to give the following compounds.

(+)-5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

White amorphous

[α]_(D) ²⁵ =+234° (methanol, c=0.2)

Purity; more than 99% ee, determined by HPLC using an optical acitivecolumn

HPLC conditions;

Mobile phase; n-hexane:ethanol:diethylamine =950:50:1

Flow rate; 1.0 ml/min.

Column; CHIRALCEL OD, 25 cm×0.46 cm (manufactured by Daicel ChemicalInd. Ltd.)

Concentration of sample; 0.1% in methanol

Retention time; 34 minutes

¹ H-NMR (DMSO-d₆) δ; 0.85-1.20, 1.56-4.06, 4.94-5.21 (total 13H, m),2.36 (3H, s), 6.79 (1H, d, J=7.6 Hz), 7.12-7.60 (8H, m), 7.62 (2H, d,J=8.4 Hz), 8.00 (1H, d, J=7.6 Hz), 10.43 (1H, s), 11.80 (1H, brs)

(-)-5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

White amorphous

[α]_(D) ²⁵ =-23.1° (methanol, c=0.2)

Purity; more than 99% ee, determined by HPLC using an optical activecolumn, and the conditions are the same as above except that theretention time is 40 minutes.

¹ H-NMR (DMSO-d₆) δ; 0.83-1.19, 1.55-4.06, 4.94-5.20 (total 13H, m),2.36 (3H, s), 6.80 (1H, d, J=7.8 Hz), 7.12-7.60 (8H, m), 7.63 (2H, d,J=8.5 Hz), 8.00 (1H, d, J=7.8 Hz), 10.44 (1H, s), 11.74 (1H, brs)

Pharmacological Test

Experiment 1: V₁ receptor binding assay

Using rat liver plasma membrane preparations prepared according toIchihara's method [cf: Akira Ichihara, J. Bio. Chem., 258, 9283 (1983)],the plasma membrane (50000 dpm, 2×10⁻¹⁰ M) of [³ H]-Arg-vasopressin anda test compound (60 μg, 10⁻⁸ -10⁻⁴ M) are incubated at 37° C. for 10minutes in 100 mM Tris-HCl buffer (pH: 8.0, 250 μl) containing 5 mMMgCl₂, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filteredthree times using the glass filter (GF/F) so as to separate the membranepreparation combined with vasopressin and then washed with the buffer (5ml). This glass filter is taken out and mixed with liquid scintillationcocktail. The amount of [³ H]-vasopressin combined with the membrane ismeasured by liquid scintillation counter and the rate of the inhibitoryeffect of the test compound is estimated according to the followingequation. ##EQU1## C¹ : The amount of [³ H]-vasopressin combined withthe membrane in the presence of the test compound (in prescribedamount).

C⁰ : The amount of [³ H]-vasopressin combined with the membrane in theabsence of the test compound.

B¹ : The amount of [³ H]-vasopressin combined with the membrane in thepresence of the excess amount of vasopressin (10⁻⁶ M).

The results are expressed as IC₅₀ values, which is the concentration ofthe test compound required to achieve the inhibitory effect in the rateof 50%.

The results are shown in the following Table 10.

Test Compound

1. 1-(4-Benzoylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

2. 1-[4-(3-Chlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

3. 1-[4-(3-Methoxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

4. 1-[4-(3-Cyanobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

5. 1-[4-(3-Aminobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

6. 1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

7. 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

8.1-[4-(2-Trifluoromethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

9. 1-[4-(2-Nitrobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline.

10. 1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

11. 1-[4-(3,3-Dimethylbutyrylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

12. 1-[4-(2-Cyclohexylacetylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

13. 1-[4-(2-Phenylacetylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

14. 1-(4-Cyclohexylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

15. 1-(4-Cycloheptylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

16. 1-(4-Cyclooctylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

17.1-(4-Tricyclo[3.3.1.1]decanylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

18. 1-[4-(α-Naphthylcarbonylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

19. 1-[4-(3-Thenoyl)benzoyl]-1,2,3,4-tetrahydroquinoline

20. 1-[2-(β-Naphthylcarbonylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

21. 1-[4-(4-Methoxyanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

22. 1-[4-(2-Methylanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

23. 1-[4-(3-Chloroanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

24.1-[4-(3,5-Dichloroanilinocarbonyl)benzoyl]-1,2,3,4-tetrahydroquinoline

25. 1-(4-Cyclohexylaminocarbonylbenzoyl)-1,2,3,4-tetrahydroquinoline

26.1-(4-Cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

27. 1-(4-Benzoylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

28.1-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

29.1-[4-(3-Methoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

30.1-[4-(3-Chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

31. 1-[4-(3-Cyanobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

32.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

33.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

34.1-(4-Cyclohexylcarbonylaminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine

35. 1-(4-Benzoylaminobenzoyl)-1,2,3,4,5,6-hexahydrobenzazocine

36. 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

37.1-[4-(3-Methoxybenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

38.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

39.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

40.1-(4-Cyclohexylcarbonylaminobenzoyl)-1,2,3,5-tntrahydro-4,1-benzoxazepine

41.1-[4-(3-Methylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzoxazepine

42.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzoxazepine

43.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzoxazepine

44. 3-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

45. 3-Methyl-1-(4-benzoylaminobenzoyl)-1,2,3,4-tetrahydroquinoline

46.3-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

47.3-Methyl-1-[4-(3-methoxybenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

48.3-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

49.3-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

50.4-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-1,2,3,4-tetrahydroquinoxalin

51.4-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoxaline

52.4-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoxaline

53.4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoxaline

54.2-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

55.4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

56. 1-[4-(2-Bromobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

57. 1-[4-(3-Nitrobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

58.1-[4-(3-Trifluoromethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

59.1-[4-(3-Ethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

60.1-[4-(3,5-Dimethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

61.1-[4-(2-Chloro-4-nitrobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

62.1-[4-(2,4-Dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

63.1-[4-(2-Chloro-6-fluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

64.1-[4-(2,6-Dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

65.1-[4-(2-Chloro-4-aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

66.1-[4-(2-Chloro-4-acetylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

67. 1-[4-(3-Aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

68.1-{4-[2-(4-Isopropylaminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

69.1-[4-(3-Hydroxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

70.1-{4-[2-(4-Aminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

71.1-{4-[2-(2-Diethylaminoethoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinehydrochloride

72.1-{4-[2-(4-Acetylaminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

73.1-{4-[2-(6-Phthalimidohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

74.1-{4-[2-(6-Morpholinohexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

75.1-{4-[2-(6-[4-Methyl-1-piperazinyl]hexyloxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepinedihydrochloride

76.1-(3-Methoxy-4-cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

77.1-(3-methoxy-4-benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

78.1-[3-Methyl-4-(2-methylbenzoylamino)benzoy]-2,3,4,5-tetrahydro-1H-benzazepine

79.4-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

80.4-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

81.4-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

82.4-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

83.4-Methyl-1-[4-(3-methoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

84.4-Methyl-1-[4-(3-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

85.4-Methyl-1-[4-(2,3,5-trichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

86.4-propyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepinehydrochloride

87.5-Methyl-1-(4-benzoylaminobenzoyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

88.5-Methyl-1-(4-cyclohexylcarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

89.5-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

90.5-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

91.5-Methyl-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

92.4-Methyl-1-[3-methoxy-4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

93.3-(1-Pyrrolidinyl)-1-[4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

94.6-Methyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

95.6-Methoxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

96.3-Hydroxymethyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

97.4-Methylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

98.3-Amino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

99.3-Acetylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

100.4-Dimethylamino-1-[4-(3,5-dichlorobenzoylino)benzoyl]-1,2,3,4-tetrahydroquinoline

101.1-[4-(2-t-Butylaminoacetylamino)benzoyl]-2,3,4,5-tetrahydroquinoline-1H-benzazepine

102.1-{4-[2-(N-Cyclohexyl-N-ethyl)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

103. 1-{4-[2-(1-Piperidinyl)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

104.1-[4-(2-Phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

105.1-[4-(2-Phthalimidoacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

106.1-{4-[2-(1,1-Dimethyl-2-phenoxyethyl)aminoacetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

107.1-{4-[2-(3-Methylphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

108.1-{4-[2-(3-Methoxyanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

109.1-{4-[2-(β-Naphthyloxy)acetyamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

110.1-{4-[2-(4-Methylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

111.1-{4-[2-(3-Methoxyphenoxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

112.1-[4-(4-Pyridylcarbonylaminobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

113.1-{4-[2-(2,4-Dimethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

114.1-{4-[2-(N-Ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

115.1-{4-[2-(N-Allylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

116.1-{4-[2-(2-Chloroanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

117.1-{4-[2-(4-Acetyloxybutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

118.1-[4-(2-Carboxymethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

119.1-[4-(2-Carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

120.1-{4-[2-(4-Hydroxybutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

121.1-[4-(2-Ethoxycarbonylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

122.6-Fluoro-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

123.6-Fluoro-1-{4-[di-(3,5-dichlorobenzoyl)amino]benzoyl}-1,2,3,4-tetrahydroquinoline

124.1-[4-(2-Diethylaminocarbonylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

125.1-{4-[2-(2-[(N-(2-hydroxyethyl)-N-methylamino]ethoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzoazepinehydrochloride

126.1-[4-(2-Methylanilinocarbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

127.1-[4-(2-Chlorophenylsulfonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

128.1-{4-[2-(4-Aminomethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

129.1-{4-[2-(N-Phenyl-N-(3-acetylaminopropyl)amino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

130.1-{4-[2-(N-Phenyl-N-propargylamino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

131.4-(N-Methyl-N-ethylamino)-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

132.5-Dimethylamino-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

133.4-Dimethylamino-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

134.5-Dimethylamino-1-[3-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

135.1-[4-(2,3-Dimethylbenzoylamino)benzoyl]-4-ethyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

136.1-[4-(3,5-Dichlorobenzoylamino)benzoyl]-4-isopropyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

137.1-[4-(2-Methylbenzoylamino)benzoyl]-5-methyl-1,2,3,4,5,6-hexahydro-1,5-benzodiazocine

138.1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydro-5,1-benzoxazepine

139.5-Oxo-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

140.4-Methyl-1-[2-chloro-4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

141.5-Methylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

142.5-(N-Acetyl-N-methylamino)-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

143.5-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

144.4-Dimethylamino-1-[3-methoxy-4-(2,3-dimethylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

145.4-Dimethylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

146.4-Dimethylaminomethyl-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

147.5-Methoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

148.4-Methyl-1-[3-methyl-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

149.5-Methoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

150.4-Dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

151.4-Acetyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4-tetrahydroquinoline

152.5-Hydroxyimino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

153.5-Acetyloxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

154.5-Ethoxycarbonylmethoxy-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

155.4-Allylamino-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

156.5-Dimethylamino-1-[3-methoxy-4-(2,3,5-trichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

157.4-[4-(2-Methylbenzoylamino)benzoyl]-3,4-dihydro-2H-1,4-benzothiazine

158.5-Dimethylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

159.5-Dimethylamino-1-[4-(2-methylanilinocarbonyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

160.5-Ethoxycarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

161.5-(4-dimethylaminobutoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

162.5-Carboxymethoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

163.5-Dimethylaminocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

164.5-Carbamoylmethoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

165.5-Dimethylamino-1-[3-ethoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

166.5-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1,5-benzothiazepine

167.5-Amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

168.5-Dimethylamino-1-[3-hydroxy-4-[2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

169.5-n-Propylamino-1-[4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

170.5-Dimethylamino-1-[3-benzyloxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

171.5-[4-(2-Methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1,5-benzothiazepin-1-oxide

172.5-[3-(Phthalimid-1-yl)-propoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

173.5-(3-Aminopropoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

174.5-(3-Acetylaminopropoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

175.5-Dimethylamino-1-[2-chloro-4-(2-t-butylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

176.5-Methylamino-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

177.5-Dimethylamino-1-[2-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

178.5-Hydroxy-1-[4-(3,5-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

179.5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

180.5-Dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

181.5-Methylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

182.5-Methylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

183.5-Dimethylamino-1-[2-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

184.5-Dimethylamino-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

185.5-Methylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl-2,3,4,5-tetrahydro-1H-benzazepine

186.5-Cyclopropylamino-1-[2-chloro-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

187.5-Dimethylaminocarbonyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

188.5-Dimethylamino-1-[4-(2-trifluoromethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

189.5-Dimethylamino-1-[3-(2-chlorobenzoyloxy)-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

190.5-(N-Methyl-N-Allylamino)-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

191.5-Carbamoyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

192.1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzothiazepine

193.4-Oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

194.1-[4-(2-Methylbenzoylamino)benzoyl]-1,2,3,5-tetrahydro-4,1-benzothiazepine-1,1-dioxide

195.5-Methylaminocarbonylmethoxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

196.5-Methylaminocarbonyloxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahyro-1H-benzazepine

197.5-Dimethylamino-1-[2-dimethylamino-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

198.5-Methylamino-1-[2-chloro-4-(2-trifluoromethylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

199.5-Cycloropropylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

200.5-Cyclopropylamino-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

201.5-Allylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

202.5-(1-Piperidinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

203.5-(4-Benzyl-1-piperazinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

204.5-(1-Pyrrolidinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

205.5-(4-Acetyl-1-piperazinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

206.5-(4-Methyl-1-piperazinyl)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

207. 1-[4-(2-Chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine

208.5-Methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

209.5-Methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

210.5-Hydroxy-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

211.5-(1-Morpholino)-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

212.5-Dimethylamino-1-[4-(2-fluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

213.5-Dimethylamino-1-[4-(2,4-difluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

214.4-Hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

215.5-Hydroxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

216.5-Dimethylamino-4-hydroxy-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

217. 1-[4-(2-Methylbenzoylamino)benzoyl]-1,2-dihydroquinoline

218.5-Dimethylamino-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine(the compound of Example 979)

219.5-Dimethylamino-1-[2-methyl-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

220.5-Dimethylamino-1-[2-methyl-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

221.5-Methylamino-1-{2-chloro-4-[2-(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

222.5-Hydroxy-1-{2-chloro-4-[2-(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

223.5-Dimethylamino-1-[2-fluoro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

224.5-Methylamino-4-hydroxy-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine.hydrochloride

225.5-Hydroxymethyl-5-hydroxy-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

226.5-Dimethylamino-1-[2-fluoro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

227.5-Dimethylamino-1-[3-methyl-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

228.5-(N-Methyl-N-ethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

229.5-Ethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

230.5-Dimethylamino-1-[4-(3,5-difluorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

231.5-Acetyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

232.5-Dimethylamino-1-[3-fluoro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

233.4,4-Dimethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

234.5-Acetyloxyimino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

235.5-Methylsulfonyloxymethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

236.5,5-Epoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

237.5-Hydroxymethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

238.5-Hydroxy-1-[2-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

239.5-Dimethylamino-1-[4-(2-carbamoylmethoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

240.5-Hydroxy-6-methyl-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

241.5-(2-Dimethylaminoethyl)amino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

242.5-Hydroxymethyl-5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

243.5-Methylaminomethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

244.5-Aminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

245.5-[N-Methyl-N-(3-methoxy-2-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

246.5-[N-Methyl-N-(3-diethylamino-2-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

247.5-Dimethylamino-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

248.5-Dimethylamino-1-[3-methoxy-4-(2,4-dichlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

249.5-Dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine.hydrochloride

250.5-Azidomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

251.7-[4-(2-Chlorobenzoylamino)benzoyl]-1-methyl-1,2,3,4a,5,6,7,11b-octahydro-3-oxo[1]benzazepino[4,5-b]-[1,4]oxazine

252.5-Benzylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

253.5-Amino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

254.5-Dimethylamino-4-methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

255.5-Acetylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

256.5-Hydroxy-4-methyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

257.5-[2-(2-Pyridyl)ethylamino]-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

258.5-(N-Methyl-N-methanesulfonylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

259.5-(N-Methyl-N-benozylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

260.5-Ethoxycarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

261.5-Methyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

262.5-(N-Methyl-N-ethoxycarbonylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

263.5-Cyclopentylamino-1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

264.5-[N-Methyl-N-(2,3-dihydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

265.5-(N-Methyl-N-cyanomethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

266.5-(N-Methyl-N-carbamoylmethylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

267.5-{N-Methyl-N-[3-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

268.5-Dimethylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

269.5-Formylaminomethyl-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

270.5-[N-Methyl-N-(3-acetyloxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

271.5-[N-Methyl-N-(3-hydroxypropyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

272. Potassium{1-[2-chloro-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}imino-o-sulfonate

273.5-Dimethylamino-1-(4-benzoylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

274.5-(1-Benzyl-4-piperidinyl)amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

275.5-(2-Dimethylaminoacetyloxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

276.5-Dimethylamino-1-[4-(3-methoxybenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

277.5-[(4-Methyl-1-piperazinyl)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

278.5-Morpholinocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

279.5-Thiomorpholinocarbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

280.5-Anilinocarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

281.5-(1-Oxothiomorpholino)carbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

282.5-Hydrazino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

283.5-Methylaminocarbonylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

284.5-[(2-α-Carbamoyl-1-pyrrolidinyl)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

285.5-(Carbamoylmethylaminocarbonylmethoxy)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

286.5-(1,1-Dioxothiomorpholino)carbonylmethoxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

287.7-Chloro-5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

288.5-[(4-Acetyl-1-piperazinyl)carbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

289.5-Dimethylamino-1-[4-(3-nitrobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

290.5-[(4-Pyridyl)methylaminocarbonylmethoxy]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

291.5-[2-(Methylamino)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

292.5-Dimethylamino-1-[4-(3-aminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

293.5-{[N-Methyl-N-(2-hydroxyethyl)amino]carbonylmethoxy}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

294.5-Dimethylamino-1-[3-(2-diethylaminoethoxy)-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

295.5-[N-Methyl-N-(dimethylaminocarbonylmethyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

296. Potassium2-[N-methyl-N-{1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepin-5-yl}amine]acetate

297.5-{N-Methyl-N-[2-(1-imidazolyl)acetyl]amino}-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

298.5-Dimethylamino-1-[4-(2-dimethylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

299.5-[(2-Aminoacetyl)amino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

300.5-Dimethylamino-1-[4-(3-acetylaminobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

301.5-(2-t-Butoxycarbonylaminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

302.5-Methylamino-7-chloro-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

303.5-Dimethylamino-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

304.5-Dimethylamino-7-chloro-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

305.5-Dimethylamino-1-[4-(phenylacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

306.5-Dimethylamino-1-[4-(3-phenylpropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

307. 5-Methylamino-7-chloro-1-{4-[(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

308.5-Dimethylamino-7-chloro-1-{4-[(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

309.5-Dimethylamino-1-[4-(2-bromobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

310.5-Cyclopropylamino-7-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

311.5-Cyclopropylamino-7-chloro-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

312.5-hydroxy-1-{4-[2-(4-isopropylaminobutoxy)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

313.5-Dimethylaminocarbonylmethoxy-1-{4-[(N-ethylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

314.5-(N-Methyl-N-ethylamino)-1-[2-chloro-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

315.5-Dimethylamino-1-{4-[(2-chloroanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

316.5-Dimethylamino-1-{4-[(2-methylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

317.5-Dimethylamino-1-{4-[(N-methyl-2-methylanilino)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine

318.5-Methylamino-9-chloro-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

319.5-Dimethylamino-1-[4-(phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

320.6-Methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-1,2,3,4,5,6-hexahydrobenzazocine

321.5-Methylamino-7-chloro-1-[3-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

322.5-Cyclopropylamino-7-chloro-1-[3-methoxy-4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

323.5-Methylamino-7-chloro-1-[3-methoxy-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

                  TABLE 10                                                        ______________________________________                                        Test                   Test                                                   Comp.    IC.sub.50     Comp.   IC.sub.50                                      No.      (μM)       No.     (μM)                                        ______________________________________                                        26       0.071          78     0.10                                           27       0.095          88     0.34                                           28       0.056          90     0.38                                           29       0.15          114     0.011                                          30       0.15          115     0.012                                          32       0.30          116     0.04                                           33       0.092         117     0.22                                           36       0.41          119     0.049                                          46       0.40          120     0.29                                           56       0.025         121     0.45                                           57       0.46          124     0.15                                           58       0.40          125     0.091                                          59       0.31          130     0.023                                          60       0.18          143     0.15                                           62       0.098         147     0.28                                           63       0.14          161     0.14                                           64       0.069         163     0.22                                           67       0.34          164     0.15                                           68       0.013         172     0.26                                           69       0.066         173     0.15                                           70       0.041         174     0.14                                           71       0.18          187     0.45                                           72       0.12          188     0.47                                           74       0.10          192     0.054                                          75       0.069         193     0.17                                           76       0.042         195     0.17                                           77       0.085         196     0.40                                           207      0.16          284     0.29                                           208      0.11          285     0.18                                           209      0.074         286     0.40                                           214      0.27          287     0.064                                          215      0.13          288     0.26                                           222      0.096         290     0.21                                           231      0.16          293     0.19                                           235      0.088         298     0.29                                           236      0.16          302     0.071                                          238      0.39          303     0.19                                           244      0.23          304     0.21                                           250      0.19          307     0.024                                          252      0.36          308     0.11                                           255      0.046         309     0.43                                           256      0.049         310     0.065                                          266      0.29          311     0.078                                          269      0.48          312     0.056                                          274      0.11          313     0.032                                          275      0.18          315     0.38                                           277      0.23          316     0.47                                           278      0.30          321     0.059                                          279      0.15          322     0.044                                          280      0.47          323     0.064                                          281      0.18                                                                 ______________________________________                                    

Pharmacological Test

Experiment 2: V₂ receptor binding assay

Using rat kidney plasma membrane preparations prepared according to O.Hechter's method [cf: J. Bio. Chem., 253, 3211 (1978)], the plasmamembrane (100000 dpm, 4×10⁻¹⁰ M) of [³ H]-Arg-vasopressin and a testcompound (0.6 mg, 10⁻¹⁰ -10⁻⁵ M) are incubated at 4° C. for 3 hours in100 mM Tris-HCl buffer (pH: 8.0, 250 μl) containing 5 mM MgCl₂, 1 mMEDTA and 0.1% BSA. After incubation, the mixture is filtered using theglass filter (GF/F) so as to separate the membrane preparation combinedwith vasopressin and then washed twice with the buffer (5 ml). Thisglass filter is taken out and mixed with liquid scintillation cocktail.The amount of [³ H]-vasopressin combined with the membrane is measuredby liquid scintillation counter and the rate of the inhibitory effect ofthe test compound is estimated according to the following equation.##EQU2## C¹ : The amount of [³ H]-vasopressin combined with the membranein the presence of the test compound (in prescribed amount).

C⁰ : The amount of [³ H]-vasopressin combined with the membrane in theabsence of the test compound.

B¹ : The amount of [³ H]-vasopressin combined with the membrane in thepresence of the excess amount of vasopressin (10⁻⁶ M).

The results are expressed as IC₅₀ values, which is the concentration ofthe test compound required to achieve the inhibitory effect in the rateof 50%.

The results are shown in the following Table 11.

                  TABLE 11                                                        ______________________________________                                        Test                   Test                                                   Comp.    IC.sub.50     Comp.   IC.sub.50                                      No.      (μM)       No.     (μM)                                        ______________________________________                                        1        0.98          28      0.018                                          2        0.20          29      0.069                                          3        0.40          30      0.029                                          4        0.58          31      0.098                                          5        1.2           32      0.016                                          6        0.076         33      0.007                                          7        0.20          34      0.049                                          8        0.32          35      0.20                                           9        0.53          36      0.028                                          10       0.082         37      0.16                                           11       1.05          38      0.029                                          12       1.97          39      0.071                                          13       1.02          40      0.33                                           14       0.23          41      0.20                                           15       0.13          42      0.063                                          16       0.17          43      0.17                                           17       0.23          44      0.050                                          18       1.0           45      0.19                                           19       1.7           46      0.018                                          20       1.4           47      0.20                                           21       1             48      0.021                                          22       0.33          49      0.063                                          23       1.07          50      1.3                                            24       1.09          51      0.40                                           25       1.67          52      0.32                                           26       0.025         53      1.6                                            27       0.070         54      0.11                                           55       0.091         86      0.58                                           56       0.037         87      0.046                                          57       0.16          88      0.021                                          58       0.14          89      0.035                                          59       0.24          90      0.014                                          60       0.15          91      0.005                                          61       0.090         92      0.41                                           62       0.023         93      0.52                                           63       0.046         94      0.095                                          64       0.007         95      0.089                                          65       0.081         96      0.039                                          66       0.45          97      0.024                                          67       0.050         98      0.45                                           68       0.19          99      1.6                                            69       0.12          100     0.011                                          70       0.012         101     0.60                                           71       0.085         102     0.29                                           72       0.16          103     0.54                                           74       0.51          104     0.37                                           75       0.30          105     0.72                                           76       0.017         106     0.44                                           77       0.090         107     0.032                                          78       0.084         108     0.12                                           79       0.53          109     0.49                                           80       0.070         110     0.044                                          81       0.15          111     0.087                                          82       0.17          112     0.29                                           83       0.73          113     0.28                                           84       0.11          114     0.006                                          85       0.068         115     0.006                                          116      0.039         146     0.056                                          117      0.24          147     0.009                                          118      0.55          148     0.34                                           119      0.059         149     0.004                                          120      0.28          150     0.14                                           121      0.18          151     0.18                                           122      0.10          152     0.039                                          123      0.10          153     0.063                                          124      0.13          154     0.063                                          125      0.28          155     0.028                                          126      0.062         156     0.15                                           127      0.99          157     0.38                                           128      0.23          158     0.018                                          129      0.29          159     0.020                                          130      0.007         160     0.020                                          131      0.027         161     0.009                                          132      0.013         162     0.059                                          133      0.022         163     0.009                                          134      0.048         164     0.010                                          135      0.081         165     0.098                                          136      0.18          166     0.070                                          137      0.41          167     0.032                                          138      0.11          168     0.083                                          139      0.10          169     0.071                                          140      0.024         170     0.25                                           141      0.010         171     0.87                                           142      0.008         172     0.023                                          143      0.008         173     0.008                                          144      0.02          174     0.007                                          145      0.06          175     0.038                                          176      0.004         206     0.088                                          177      0.15          207     0.045                                          178      0.012         208     0.007                                          179      0.040         209     0.004                                          180      0.034         210     0.004                                          181      0.038         211     0.12                                           182      0.005         212     0.035                                          183      0.26          213     0.033                                          184      0.023         214     0.058                                          185      0.005         215     0.006                                          186      0.030         216     0.91                                           187      0.029         217     0.37                                           188      0.039         218     0.022                                          189      0.087         219     0.023                                          190      0.082         220     0.026                                          191      0.009         221     0.024                                          192      0.011         222     0.010                                          193      0.036         223     0.022                                          194      0.21          224     0.38                                           195      0.010         225     0.030                                          196      0.013         226     0.019                                          197      0.99          227     0.029                                          198      0.040         228     0.029                                          199      0.019         229     0.029                                          200      0.024         230     0.020                                          201      0.023         231     0.007                                          202      0.14          232     0.020                                          203      0.070         233     0.15                                           204      0.11          234     0.14                                           205      0.074         235     0.006                                          236      0.006         267     0.12                                           237      0.041         268     0.018                                          238      0.020         269     0.003                                          239      0.17          270     0.046                                          240      0.022         271     0.030                                          241      0.006         272     0.40                                           242      0.17          273     0.027                                          243      0.40          274     0.024                                          244      0.018         275     0.018                                          245      0.059         276     0.032                                          246      0.027         277     0.016                                          247      0.048         278     0.013                                          248      0.060         279     0.008                                          250      0.12          280     0.045                                          251      0.094         281     0.011                                          252      0.063         282     0.38                                           253      0.052         283     0.096                                          254      0.016         284     0.019                                          255      0.005         285     0.008                                          256      0.004         286     0.019                                          257      0.045         287     0.007                                          258      0.20          288     0.015                                          259      0.25          289     0.071                                          260      0.13          290     0.021                                          261      0.011         291     0.13                                           262      0.029         292     0.18                                           263      0.053         293     0.065                                          264      0.030         294     0.33                                           265      0.025         295     0.026                                          266      0.013         296     0.25                                           297      0.051         311     0.013                                          298      0.10          312     0.29                                           299      0.22          313     0.012                                          300      0.48          314     0.096                                          301      0.14          315     0.025                                          302      0.011         316     0.060                                          303      0.025         317     0.072                                          304      0.024         318     0.060                                          305      0.038         319     0.058                                          306      0.077         320     0.039                                          307      0.010         321     0.012                                          308      0.023         322     0.025                                          309      0.015         323     0.014                                          310      0.008                                                                ______________________________________                                    

Experiment 3: Anti-antidiuretic activity (effect on endogenous ADH)

A test compound or solvent (dimethylformamide) is administered into acaudal vein of untreated, unrestrained SD rats (male, weight: 300-350 g)and the amount of urine, which is spontaneously excreted for a period of2 hours thereafter, is collected and measured by using a metabolicgauge. During this measurement, the rats are allowed to take water andfeed freely.

The amount of urine of control rats (solvent-treated group) is regardedas 100%, and the results are expressed as ED₃ value, which is the doseof the test compound to be required to excrete the urine by three timesthan that of the control rats. The results are shown in the followingTable 12.

                  TABLE 12                                                        ______________________________________                                        Test compound No.                                                                              ED.sub.3 (mg/kg)                                             ______________________________________                                         6               10                                                            33              1.9                                                          178              4.2                                                          249               0.4 *.sup.)                                                 ______________________________________                                         *.sup.) : Physicological saline solution was used as a solvent instead of     dimethylformamide.                                                       

Using the suitable starting materials, the compounds of the followingTable 13 are obtained in the same manner as in Examples 1 and 382.##STR1148##

EXAMPLE 1190 ##STR1149##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 210°-213° C.

Form: Free

EXAMPLE 1191 ##STR1150##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 184.5°-186° C.

Form: Free

EXAMPLE 1192 ##STR1151##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 201.5°-202.5° C.

Form: Free

EXAMPLE 1193 ##STR1152##

Crystalline form: White powder

Recrystallization solvent: Dichloromethane/diethyl ether

Melting Point: 159°-162° C. (decomposed)

Form: Free

EXAMPLE 1194 ##STR1153##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/dichloromethane

Melting Point: 237°-240° C.

Form: Free

EXAMPLE 1195 ##STR1154##

Crystalline form: White powder

Recrystallization solvent: Diethyl ether/dichloromethane

Melting Point: 269°-272.5° C.

Form: Free

EXAMPLE 1196 ##STR1155##

Crystalline form: Colorless prisms

Recrystallization solvent: Ethanol/dichloromethane

Melting Point: 201°-202° C.

Form: Free

EXAMPLE 1197 ##STR1156##

Crystalline form: White powder

Recrystallization solvent: Methanol

Melting Point: 204°-206° C.

Form: Free

EXAMPLE 1198 ##STR1157##

Crystalline form: Colorless amorphous

NMR analysis: 313)

Form: Free

EXAMPLE 1199 ##STR1158##

Crystalline form: Colorless amorphous

NMR analysis: 314)

Form: Free

EXAMPLE 1200 ##STR1159##

Crystalline form: Colorless amorphous

NMR analysis: 315)

Form: Free

EXAMPLE 1201 ##STR1160##

Crystalline form: Colorless amorphous

NMR analysis: 316)

Form: Free

EXAMPLE 1202 ##STR1161##

Crystalline form: Colorless amorphous

NMR analysis: 317)

Form: Free

EXAMPLE 1203 ##STR1162##

Crystalline form: Light brown amorphous

NMR analysis: 318)

Form: Hydrochloride

EXAMPLE 1204 ##STR1163##

Crystalline form: Colorless amorphous

NMR analysis: 319)

Form: Free

EXAMPLE 1205 ##STR1164##

Crystalline form: Colorless amorphous

NMR analysis: 320)

Form: Hydrochloride

EXAMPLE 1206 ##STR1165##

Crystalline form: Colorless amorphous

NMR analysis: 321)

Form: Hydrochloride

EXAMPLE 1207 ##STR1166##

Crystalline form: Colorless amorphous

NMR analysis: 322)

Form: Free

EXAMPLE 1208 ##STR1167##

Crystalline form: Light yellow prisms

Recrystallization solvent: Ethyl acetate/n-hexane

Melting Point: 187°-189° C.

Form: Free

EXAMPLE 1209 ##STR1168##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 227°-231° C.

Form: Free

EXAMPLE 1210 ##STR1169##

Crystalline form: White powder

Recrystallization solvent: Methanol/diethyl ether

Melting Point: 191°-192° C.

Form: Free

EXAMPLE 1211 ##STR1170##

Crystalline form: Colorless amorphous

NMR analysis: 323)

Form: Free

EXAMPLE 1212 ##STR1171##

Crystalline form: Colorless amorphous

NMR analysis: 324)

Form: Free

EXAMPLE 1213 ##STR1172##

Crystalline form: White amorphous

NMR analysis: 325)

Form: Hydrochloride

313) ¹ H-NMR (CDCl₃) δ; 1.40-2.30 (4H, m), 2.36 (3H, s), 2.60-2.92 (2H,m), 4.35-5.18 (2H, m), 6.69-6.87 (1H, m), 6.87-7.04 (1H, m), 7.05-8.06(8H, m), 8.25-8.60 (1H, m)

314) ¹ H-NMR (CDCl₃) δ; 1.43-2.26 (4H, m), 2.38 (3H, s), 2.42 (3H, s),2.61-2.91 (1H, m), 2.91-3.40 (1H, m), 4.49-5.08 (2H, m), 6.40-7.68 (10H,m), 7.68-7.93 (1H, m)

315) ¹ H-NMR (CDCl₃) δ; 1.32-2.25 (4H, m), 2.25-2.54 (3H, m), 2.59-3.42(2H, m), 4.45-5.08 (2H, m), 6.40-7.80 (10H, m), 8.00-8.38 (1H, m)

316) ¹ H-NMR (CDCl₃) δ; 1.42-1.89 (2H, m), 1.90-2.30 (2H, m), 2.57-2.95(2H, m), 3.36-3.64 (3H, m), 4.51-5.17 (2H, m), 6.52-7.80 (10H, m),8.11-8.41 (1H, m)

317) ¹ H-NMR (CDCl₃) δ; 1.18-2.25 (4H, m), 2.25-2.59 (3H, m), 2.59-2.88(1H, m), 2.88-4.32 (1H, m), 4.32-5.05 (2H, m), 6.44-8.08 (10H, m),8.52-9.00 (1H, m)

318) ¹ H-NMR (DMSO-d₆) δ; 1.35-2.45 (7H, m), 2.6-3.0 (8H, m), 3.2-4.2(6H, m), 4.45-4.85 (2H, m), 6.75-7.7 (11H, m)

319) ¹ H-NMR (CDCl₃) δ; 1.20-2.89, 3.22-4.33, 4.48-5.05, 5.75-6.32[total 17H, m {2.45 (s)}], 6.52-7.78 (10H, m), 8.10-8.71 (1H, m)

320) ¹ H-NMR (DMSO-d₆) δ; 1.49-3.05 [11H, m {2.35 (s), 2.40 (s)}],3.71-5.04 (3H, m), 5.28-5.88 (1H, m), 6.64-7.98 (10H, m), 8.58 (3H,brs), 10.32, 10.48 (total 1H, each s)

321) ¹ H-NMR (DMSO-d₆) δ; 1.50-3.70 [17H, m {2.36, 2.40 (each s), 2.87,2.89, 2.94 (each s)}], 4.05-5.08 (3H, m), 5.90-6.28 (1H, m), 6.62-7.98(10H, m), 10.36, 10.52 (total 1H, each brs), 10.94 (1H, brs)

324) ¹ H-NMR (CDCl₃) δ; 1.53-2.91 [14H, m {2.42, 2.47 (each s)}],3.09-4.27 (5H, m), 4.70-5.12 (1H, m), 5.89-6.36 (1H, m), 6.57-7.94 (11H,m)

323) ¹ H-NMR (CDCl₃) δ; 1.32-2.23 (2H, m), 2.23-2.68 (7H, m), 2.68-3.84(8H, m), 3.84-5.23 (4H, m), 6.47-7.88 (11H, m)

324) ¹ H-NMR (CDCl₃) δ; 1.45-2.32 (5H, m), 2.44 (3H, s), 2.63-3.21 (1H,m), 3.40-5.01 (4H, m), 6.28-7.93 (10H, m), 8.10-8.43 (1H, m)

325) ¹ H-NMR (DMSO-d₆) δ; 0.71-3.46, 4.15-4.44 [total 23H, 2.35 (s),2.42 (s), 2.86 (s)], 6.71-7.88 (10H, m), 10.16-10.58 (2H, m)

What is claimed is:
 1. A benzoheterocyclic compound of the followingformula: ##STR1173## wherein R¹ is a hydrogen atom, a halogen atom, alower alkyl, an amino having optionally a lower alkyl substituent, or alower alkoxy,R² is a hydrogen atom, a halogen atom, a lower alkoxy, aphenyl(lower)alkoxy, hydroxy, a lower alkyl, an amino having optionallya lower alkyl substituent, a carbamoyl-substituted lower alkoxy, anamino-substituted lower alkoxy having optionally a lower alkylsubstituent, or a benzoyloxy which has optionally a halogen substituenton the phenyl ring, R³ is a group of the formula: ##STR1174## or a groupof the formula: ##STR1175## R⁴ is a hydrogen atom, a benzoyl which hasoptionally a halogen substituent on the phenyl ring, or a lower alkyl,R⁵ is a group of the formula: ##STR1176## wherein R¹⁶ is a halogen atom;a lower alkyl which has optionally a substituent selected from a halogenatom and hydroxy; hydroxy; a lower alkoxy; a lower alkanoyloxy; a loweralkylthio; a lower alkanoyl; carboxy; a lower alkoxycarbonyl; cyano;nitro; an amino which has optionally a substituent selected from a loweralkyl and a lower alkanoyl; phenyl; a cycloalkyl having 3 to 8 carbonatoms; a lower alkanoyloxy-substituted lower alkoxy; acarboxy-substituted lower alkoxy; a halogen-substituted lower alkoxy; acarbamoyl-substituted lower alkoxy; a hydroxy-substituted lower alkoxy;a lower alkoxycarbonyl-substituted lower alkoxy; aphthalimido-substituted lower alkoxy; an aminocarbonyl-lower alkoxyhaving a lower alkyl substituent; or a group of the formula: ##STR1177##wherein A is a lower alkylene, and R⁶ and R⁷ are the same or differentand are each a hydrogen atom, a lower alkyl having optionally a hydroxysubstituent, a lower alkanoyl, or benzoyl, or R⁶ and R⁷ may bindtogether with the nitrogen atom to which they are bonded to form a 5- or6-membered saturated heterocyclic group with or without a secondnitrogen atom or an oxygen atom wherein said heterocyclic group isselected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl and morpholino, and wherein the heterocyclic group hasoptionally a substituent selected from piperidinyl and a lower alkyl;and m is an integer of 0 to 3, a phenyl-lower alkoxycarbonyl, a loweralkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl whereinsaid cycloalkyl group has 3 to 8 carbon atoms, a cycloalkyl-carbonylwherein said cycloalkyl group has 3 to 8 carbon atoms,tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl, pyridylcarbonyl,furoyl, thenoyl, a phenoxy-lower alkanoyl which phenyl ring hasoptionally 1 to 3 substituents selected from a lower alkyl, a loweralkoxy and an amino having optionally a lower alkanoyl substituent, aphthalimido-substituted lower alkanoyl, a lower alkoxycarbonyl-loweralkanoyl, a carboxy-lower alkanoyl, a naphthyloxy-lower alkanoyl, ahalogen-substituted lower alkanoyl, a group of the formula: ##STR1178##wherein R⁸ is a hydrogen atom, a lower alkyl, a phenyl-loweralkoxycarbonyl, a carbamoyl-lower alkyl, an amino-lower alkanoyl havingoptionally a lower alkyl substituent, or a lower alkanoyl, ananilinocarbonyl which has optionally a lower alkyl substituent on thephenyl ring, phenoxycarbonyl, a phenylsulfonyl which has optionally asubstituent selected from a halogen atom and a lower alkyl on the phenylring, quinolylsulfonyl, or a group of the formula: ##STR1179## wherein Bis a lower alkylene, n is an integer of 0 or 1, and R⁹ and R¹⁰ are thesame or different and are each a hydrogen atom, a lower alkyl havingoptionally a hydroxy substituent, a cycloalkyl having 3 to 8 carbonatoms, a phenyl-lower alkyl, a lower alkanoyl, a lower alkenyl, aphenoxy-lower alkyl, a phenyl which has optionally 1 to 3 substituentsselected from an amino-lower alkyl having optionally a lower alkanoylsubstituent, a lower alkyl, a lower alkoxy and a halogen atom, aphthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl and morpholino, and wherein the heterocyclic group hasoptionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, R¹¹ is a hydrogen atom or a lower alkyl,R¹² is a cycloalkyl, or a phenyl which has optionally 1 to 3substituents selected from a lower alkoxy, a lower alkyl and a halogenatom, W is a group of the formula: --(CH₂)_(p) -- wherein p is aninteger of 3 to 5, or a group of the formula: --CH═CH--(CH₂)_(q) --wherein q is an integer of 1 to 3, the carbon atom of these groups:--(CH₂)_(p) -- and --CH═CH--(CH₂)_(q) -- being replaced by a group ofthe formula: ##STR1180## wherein R₁₃ is a hydrogen atom, a cycloalkylhaving 3 to 8 carbon atoms, or a lower alkyl, and further said--(CH₂)_(p) -- and --CH═CH--(CH₂)_(q) -- groups having optionally 1 to 3substituents selected from a lower alkyl having optionally a hydroxysubstituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a loweralkanoyloxy having optionally a halogen substituent, an amino-loweralkyl having optionally a substituent selected from a lower alkyl and alower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a loweralkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of theformula: ##STR1181## an aminocarbonyloxy having optionally a lower alkylsubstituent, a lower alkoxy, a lower alkoxycarbonyl-substituted loweralkoxy, a carboxy-substituted lower alkoxy, an aminocarbonyl-loweralkoxy having optionally a lower alkyl substituent, an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, alower alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido,sulfoxyimino, a group of the formula: ##STR1182## wherein R⁸¹ is ahydrogen atom or a lower alkyl, hydrazino, pyrrolyl, an amino-loweralkanoyloxy having optionally a lower alkyl substituent, a group of theformula: ##STR1183## wherein A is as defined above, and R⁸² and R⁸³ arethe same or different and are each a hydrogen atom, a lower alkyl, acarbamoyl-substituted lower alkyl, a hydroxy-substituted lower alkyl, ora pyridyl-lower alkyl, or R⁸² and R⁸³ may bind together with thenitrogen atom to which they are bonded to form a 5- or 6-memberedsaturated heterocyclic group with or without a second nitrogen atom, anoxygen atom or a sulfur atom wherein said heterocyclic group is selectedfrom the group consisting of pyrrolidinyl, piperidinyl, piperazinyl,morpholino and thiomorpholino, and wherein the heterocyclic group hasoptionally a substituent selected from oxo, a lower alkyl, a loweralkanoyl, and carbamoyl, and a group of the formula: ##STR1184## whereinn is as defined above, and R¹⁴ and R¹⁵ are the same or different and areeach a hydrogen atom, a lower alkyl, a lower alkenyl, a lower alkanoyl,a cycloalkyl, an oxiranyl-substituted lower alkyl, a lower alkyl having1 to 2 substituents selected from a lower alkoxy, hydroxy and an aminohaving optionally a lower alkyl substituent, a phenyl-lower alkyl, apyridyl-lower alkyl, a lower alkylsulfonyl, benzoyl, a loweralkoxycarbonyl, anilinocarbonyl, an aminocarbonyl having optionally alower alkyl substituent, a cyano-substituted lower alkyl, a loweralkoxycarbonyl-substituted lower alkyl, a carbamoyl-substituted loweralkyl, a carboxy-substituted lower alkyl, atetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted substituted lower alkanoyl, animidazolyl-substituted lower alkanoyl, an amino-lower alkanoyl havingoptionally a substituent selected from a lower alkyl and a loweralkoxycarbonyl, an aminocarbonyl-lower alkyl having optionally a loweralkyl substituent, or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ maybind together with the nitrogen atom to which they are bonded to form a5- or 6-membered saturated heterocyclic group with or without a secondnitrogen atom or an oxygen atom wherein said heterocyclic group isselected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl and morpholino, and wherein the heterocyclic group mayoptionally have a substituent selected from a lower alkyl, aphenyl-lower alkyl or a lower alkanoyl, and a pharmaceuticallyacceptable salt thereof.
 2. The compound according to claim 1, whereinR¹ in the formula (1) is hydrogen atom, or a pharmaceutically acceptablesalt thereof.
 3. The compound according to claim 1, wherein R¹ in theformula (1) is a halogen atom, and a pharmaceutically acceptable saltthereof.
 4. The compound according to claim 1, wherein R¹ in the formula(1) is a lower alkyl, an amino having optionally a lower alkylsubstituent, or a lower alkoxy, and a pharmaceutically acceptable saltthereof.
 5. The compound according to claim 2, wherein R² is a hydrogenatom, and a pharmaceutically acceptable salt thereof.
 6. The compoundaccording to claim 2, wherein R² is a halogen atom, a lower alkoxy, or alower alkyl, and a pharmaceutically acceptable salt thereof.
 7. Thecompound according to claim 2, wherein R² is a phenyl-lower alkoxy;hydroxy; an amino having optionally a lower alkyl substituent; acarbamoyl-substituted lower alkoxy; an amino-substituted lower alkoxyhaving optionally a lower alkyl substituent; or a benzoyloxy havingoptionally a halogen substituent on the phenyl ring thereof, and apharmaceutically acceptable salt thereof.
 8. The compound according toclaim 3, wherein R² is a hydrogen atom, and a pharmaceuticallyacceptable salt thereof.
 9. The compound according to claim 3, whereinR² is a halogen atom, a lower alkoxy, or a lower alkyl, and apharmaceutically acceptable salt thereof.
 10. The compound according toclaim 3, wherein R² is a phenyl-lower alkoxy; a hydroxy; an amino havingoptionally a lower alkyl substituent; a carbamoyl-substituted loweralkoxy; an amino-substituted lower alkoxy having optionally a loweralkyl substituent; or a benzoyloxy having optionally a halogensubstituent on the phenyl ring thereof, and a pharmaceuticallyacceptable salt thereof.
 11. The compound according to claim 4, whereinR² is a hydrogen atom, and a pharmaceutically acceptable salt thereof.12. The compound according to claim 4, wherein R² is a halogen atom, alower alkoxy, or a lower alkyl, and a pharmaceutically acceptable saltthereof.
 13. The compound according to claim 4, wherein R² is aphenyl-lower alkoxy; a hydroxy; an amino having optionally a lower alkylsubstituent; a carbamoyl-substituted lower alkoxy; an amino-substitutedlower alkoxy having optionally a lower alkyl substituent; or abenzoyloxy having optionally a halogen substituent on the phenyl ringthereof, and a pharmaceutically acceptable salt thereof.
 14. Thecompound according to claim 5, wherein R³ is a group of the formula:--NR⁴ R⁵ (R⁴ and R⁵ are as defined in claim 1), and a pharmaceuticallyacceptable salt thereof.
 15. The compound according to claim 5, whereinR³ is a group of the formula: --CO--NR¹¹ R¹² (R¹¹ and R¹² are as definedin claim 1), and a pharmaceutically acceptable salt thereof.
 16. Thecompound according to claim 6, wherein R³ is a group of the formula:--NR⁴ R⁵ (R⁴ and R⁵ are as defined in claim 1), and a pharmaceuticallyacceptable salt thereof.
 17. The compound according to claim 6, whereinR³ is a group of the formula: --CO--NR¹¹ R¹² (R¹¹ and R¹² are as definedin claim 1), and a pharmaceutically acceptable salt thereof.
 18. Thecompound according to claim 8, wherein R³ is a group of the formula:--NR⁴ R⁵ (R⁴ and R⁵ are as defined in claim 1), and a pharmaceuticallyacceptable salt thereof.
 19. The compound according to claim 8, whereinR³ is a group of the formula: --CO--NR¹¹ R¹² (R¹¹ and R¹² are as definedin claim 1), and a pharmaceutically acceptable salt thereof.
 20. Thecompound according to claim 9, wherein R³ is a group of the formula:--NR⁴ R⁵ (R⁴ and R⁵ are as defined in claim 1), and a pharmaceuticallyacceptable salt thereof.
 21. The compound according to claim 9, whereinR³ is a group of the formula: --CO--NR¹¹ R¹² (R¹¹ and R¹² are as definedin claim 1), and a pharmaceutically acceptable salt thereof.
 22. Thecompound according to claim 14, wherein R⁴ is a hydrogen atom, and R⁵ isa group of the formula: ##STR1185## (wherein R¹⁶ and m are as defined inclaim 1), and a pharmaceutically acceptable salt thereof.
 23. Thecompound according to claim 14, wherein R⁴ is a hydrogen atom and R⁵ isa phenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-loweralkanoyl, a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has3 to 8 carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl grouphas 3 to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl,naphthylcarbonyl, pyridylcarbonyl, furoyl, thenoyl, a phenoxy-loweralkanoyl which phenyl ring has optionally 1 to 3 substituents selectedfrom a lower alkyl, a lower alkoxy and an amino having optionally alower alkanoyl substituent, a phthalimido-substituted lower alkanoyl, alower alkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, groupof the formula: ##STR1186## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1187## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl and morpholino, and wherein the heterocyclic group hasoptionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 24. The compound according to claim 14, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 25. The compoundaccording to claim 16, wherein R⁴ is hydrogen atom, and R⁵ is a group ofthe formula: ##STR1188## (wherein R¹⁶ and m are as defined in claim 1),and a pharmaceutically acceptable salt thereof.
 26. The compoundaccording to claim 16, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, groupof the formula: ##STR1189## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenysulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1190## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen or an oxygen atom wherein said heterocyclic group isselected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl and morpholino, and wherein the heterocyclic group hasoptionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 27. The compound according to claim 16, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 28. The compoundaccording to claim 7, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1191## (wherein R¹⁶ and m are as defined in claim1), and a pharmaceutically acceptable salt thereof.
 29. The compoundaccording to claim 7, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR1192## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenysulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1193## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they bond to forma 5- or 6-membered saturated heterocyclic group with or without a secondnitrogen atom or an oxygen atom wherein said heterocyclic group isselected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino and thiomorpholino, and wherein the heterocyclicgroup has optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 30. The compound according to claim 7, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 31. The compoundaccording to claim 18, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1194## (wherein R¹⁶ and m are as defined in claim1), and a pharmaceutically acceptable salt thereof.
 32. The compoundaccording to claim 18, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, groupof the formula: ##STR1195## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1196## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl and morpholino, and wherein the heterocyclic group hasoptionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 33. The compound according to claim 18, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 34. The compoundaccording to claim 20, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1197## (wherein R¹⁶ and m are as defined in claim1), and a pharmaceutically acceptable salt thereof.
 35. The compoundaccording to claim 20, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR1198## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1199## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino and thiomorpholino, and wherein the heterocyclicgroup has optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 36. The compound according to claim 20, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 37. The compoundaccording to claim 10, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1200## (wherein R¹⁶ and m are as defined in claim1), and a pharmaceutically acceptable salt thereof.
 38. The compoundaccording to claim 10, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR1201## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1202## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom, wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino and thiomorpholino, and wherein the heterocyclicgroup has optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 39. The compound according to claim 10, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 40. The compoundaccording to claim 11, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1203## (wherein R¹⁶ and m are as defined in claim1), and a pharmaceutically acceptable salt thereof.
 41. The compoundaccording to claim 11, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR1204## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1205## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino and thiomorpholino, and wherein the heterocyclicgroup has optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 42. The compound according to claim 11, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 43. The compoundaccording to claim 12, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1206## (wherein R¹⁶ and m are as defined in claim1), and a salt thereof.
 44. The compound according to claim 12, whereinR⁴ is a hydrogen atom and R⁵ is a phenyl-lower alkoxycarbonyl, a loweralkanoyl, a phenyl-lower alkanoyl, a cycloalkyl-lower alkanoyl whereinsaid cycloalkyl group has 3 to 8 carbon atoms, a cycloalkylcarbonylwherein said cycloalkyl group has 3 to 8 carbon atoms,tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl, pyridylcarbonyl,furoyl, thenoyl, a phenoxy-lower alkanoyl which phenyl ring hasoptionally 1 to 3 substituents selected from a lower alkyl, a loweralkoxy and an amino having optionally a lower alkanoyl substituent, aphthalimido-substituted lower alkanoyl, a lower alkoxycarbonyl-loweralkanoyl, a carboxy-lower alkanoyl, a naphthyloxy-lower alkanoyl, ahalogen-substituted lower alkanoyl, a group of the formula: ##STR1207##wherein R⁸ is a hydrogen atom, a lower alkyl, a phenyl-loweralkoxycarbonyl, a carbamoyl-lower alkyl, an amino-lower alkanoyl havingoptionally a lower alkyl substituent, or a lower alkanoyl, ananilinocarbonyl which has optionally a lower alkyl substituent on thephenyl ring, phenoxycarbonyl, a phenylsulfonyl which has optionally asubstituent selected from a halogen atom and a lower alkyl on the phenylring, quinolylsulfonyl, or a group of the formula: ##STR1208## wherein Bis a lower alkylene, n is an integer of 0 or 1, and R⁹ and R¹⁰ are thesame or different and are each a hydrogen atom, a lower alkyl havingoptionally a hydroxy substituent, a cycloalkyl having 3 to 8 carbonatoms, a phenyl-lower alkyl, a lower alkanoyl, a lower alkenyl, aphenoxy-lower alkyl, a phenyl which has optionally 1 to 3 substituentsselected from an amino-lower alkyl having optionally a lower alkanoylsubstituent, a lower alkyl, a lower alkoxy and a halogen atom, aphthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino and thiomorpholino, and wherein the heterocyclicgroup has optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 45. The compound according to claim 12, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 46. The compoundaccording to claim 13, wherein R⁴ is a hydrogen atom, and R⁵ is a groupof the formula: ##STR1209## (wherein R¹⁶ and m are as defined in claim1), and a pharmaceutically acceptable salt thereof.
 47. The compoundaccording to claim 13, wherein R⁴ is a hydrogen atom and R⁵ is aphenyl-lower alkoxycarbonyl, a lower alkanoyl, a phenyl-lower alkanoyl,a cycloalkyl-lower alkanoyl wherein said cycloalkyl group has 3 to 8carbon atoms, a cycloalkylcarbonyl wherein said cycloalkyl group has 3to 8 carbon atoms, tricyclo(3.3.1.1)decanylcarbonyl, naphthylcarbonyl,pyridylcarbonyl, furoyl, thenoyl, a phenoxy-lower alkanoyl which phenylring has optionally 1 to 3 substituents selected from a lower alkyl, alower alkoxy and an amino having optionally a lower alkanoylsubstituent, a phthalimido-substituted lower alkanoyl, a loweralkoxycarbonyl-lower alkanoyl, a carboxy-lower alkanoyl, anaphthyloxy-lower alkanoyl, a halogen-substituted lower alkanoyl, agroup of the formula: ##STR1210## wherein R⁸ is a hydrogen atom, a loweralkyl, a phenyl-lower alkoxycarbonyl, a carbamoyl-lower alkyl, anamino-lower alkanoyl having optionally a lower alkyl substituent, or alower alkanoyl, an anilinocarbonyl which has optionally a lower alkylsubstituent on the phenyl ring, phenoxycarbonyl, a phenylsulfonyl whichhas optionally a substituent selected from a halogen atom and a loweralkyl on the phenyl ring, quinolylsulfonyl, or a group of the formula:##STR1211## wherein B is a lower alkylene, n is an integer of 0 or 1,and R⁹ and R¹⁰ are the same or different and are each a hydrogen atom, alower alkyl having optionally a hydroxy substituent, a cycloalkyl having3 to 8 carbon atoms, a phenyl-lower alkyl, a lower alkanoyl, a loweralkenyl, a phenoxy-lower alkyl, a phenyl which has optionally 1 to 3substituents selected from an amino-lower alkyl having optionally alower alkanoyl substituent, a lower alkyl, a lower alkoxy and a halogenatom, a phthalimido-substituted lower alkyl, an amino-lower alkyl havingoptionally a lower alkanoyl substituent, a lower alkynyl, or anamino-lower alkyl having optionally a lower alkyl substituent, or R⁹ andR¹⁰ may bind together with the nitrogen atom to which they are bonded toform a 5- or 6-membered saturated heterocyclic group with or without asecond nitrogen atom or an oxygen atom wherein said heterocyclic groupis selected from the group consisting of pyrrolidinyl, piperidinyl,piperazinyl, morpholino and thiomorpholino, and wherein the heterocyclicgroup has optionally a substituent selected from a lower alkyl, a loweralkoxycarboyl and piperidinyl, and a pharmaceutically acceptable saltthereof.
 48. The compound according to claim 13, wherein R⁴ is a loweralkyl, and a pharmaceutically acceptable salt thereof.
 49. The compoundaccording to claim 22, wherein R¹⁶ is a halogen atom, or a lower alkylhaving optionally a substituent selected from a halogen atom and ahydroxy, and a pharmaceutically acceptable salt thereof.
 50. Thecompound according to claim 25, wherein R¹⁶ is a halogen atom, or alower alkyl having optionally a substituent selected from a halogen atomand a hydroxy, and a pharmaceutically acceptable salt thereof.
 51. Thecompound according to claim 31, wherein R¹⁶ is a halogen atom, or alower alkyl having optionally a substituent selected from a halogen atomand a hydroxy, and a pharmaceutically acceptable salt thereof.
 52. Thecompound according to claim 34, wherein R¹⁶ is a halogen atom, or alower alkyl having optionally a substituent selected from a halogen atomand a hydroxy, and a pharmaceutically acceptable salt thereof.
 53. Thecompound according to claim 1, wherein W is a group of the formula:--(CH₂)_(p) -- wherein p is an integer of 3 to 5, and the carbon atom ofsaid group is replaced by a group of the formula: ##STR1212## whereinR¹³ is a hydrogen atom, a cycloalkyl having 3 to 8 carbon atoms, or alower alkyl, and further said --(CH₂)_(p) -- group has optionally 1 to 3substituents selected from a lower alkyl having optionally a hydroxysubstituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a loweralkanoyloxy having optionally a halogen substituent, an amino-loweralkyl having optionally a substituent selected from a lower alkyl and alower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a loweralkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of theformula: ##STR1213## an aminocarbonyloxy having optionally a lower alkylsubstituent, a lower alkoxy, a lower alkoxycarbonyl-substituted loweralkoxy, a carboxy-substituted lower alkoxy, an aminocarbonyl-loweralkoxy having optionally a lower alkyl substituent, an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, alower alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido,sulfoxyimino, a group of the formula: ##STR1214## wherein R⁸¹ is ahydrogen atom or a lower alkyl, hydrazino, pyrrolyl, an amino-loweralkanoyloxy having optionally a lower alkyl substituent, a group of theformula: ##STR1215## wherein A is as defined above, and R⁸² and R⁸³ arethe same or different and are each a hydrogen atom, a lower alkyl, acarbamoyl-substituted lower alkyl, a hydroxy-substituted lower alkyl, ora pyridyl-lower alkyl, or R⁸² and R⁸³ may bind together with thenitrogen atom to which they are bonded to form a 5- or 6-memberedsaturated heterocyclic group with or without a second nitrogen atom, anoxygen atom or a sulfur atom wherein said heterocyclic group is selectedfrom the group consisting of pyrrolidinyl, piperidinyl, piperazinyl,morpholino and thiomorpholino, and wherein the heterocyclic group hasoptionally a substituent selected from oxo, a lower alkyl, a loweralkanoyl, and carbamoyl, and a group of the formula: ##STR1216## whereinn is as defined above, and R¹⁴ and R¹⁵ are the same or different and areeach a hydrogen atom, a lower alkyl, a lower alkenyl, a lower alkanoyl,a cycloalkyl having 3 to 8 carbon atoms, an oxiranyl-substituted loweralkyl, a lower alkyl having 1 to 2 substituents selected from a loweralkoxy, hydroxy and an amino having optionally a lower alkylsubstituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, a loweralkylsulfonyl, benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, anaminocarbonyl having optionally a lower alkyl substituent, acyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted loweralkyl, a carbamoyl-substituted lower alkyl, a carboxy-substituted loweralkyl, a tetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted lower alkanoyl, an imidazolyl-substituted loweralkanoyl, an amino-lower alkanoyl having optionally a substituentselected from a lower alkyl and a lower alkoxycarbonyl, anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ may bind together withthe nitrogen atom to which they are bonded to form a 5- or 6-memberedsaturated heterocyclic group with or without a second nitrogen atom oran oxygen atom, wherein said heterocyclic group is selected from thegroup consisting of pyrrolidinyl, piperidinyl, piperazinyl andmorpholino, and wherein the heterocyclic group may optionally have asubstituent selected from a lower alkyl, a phenyl-lower alkyl or a loweralkanoyl, and a pharmaceutically acceptable salt thereof.
 54. Thecompound according to claim 1, wherein W is a group of the formula:--CH═CH--(CH₂)_(q) -- wherein q is an integer of 1 to 3, and the carbonatom of said group is replaced by a group of the formula: ##STR1217##wherein R¹³ is a hydrogen atom, a cycloalkyl, or a lower alkyl, andfurther said --(CH═CH--(CH₂)_(q) -- group has optionally 1 to 3substituents selected from a lower alkyl having optionally a hydroxysubstituent, a lower alkoxycarbonyl, carboxy, hydroxy, oxo, a loweralkanoyloxy having optionally a halogen substituent, an amino-loweralkyl having optionally a substituent selected from a lower alkyl and alower alkanoyl, a lower alkanoyloxy-substituted lower alkyl, a loweralkyl sulfonyloxy-lower alkyl, an azido-lower alkyl, a group of theformula: ##STR1218## an aminocarbonyloxy having optionally a lower alkylsubstituent, a lower alkoxy, a lower alkoxycarbonyl-substituted loweralkoxy, a carboxy-substituted lower alkoxy, an aminocarbonyl-loweralkoxy having optionally a lower alkyl substituent, an amino-loweralkoxy having optionally a substituent selected from a lower alkyl and alower alkanoyl, a phthalimido-substituted lower alkoxy, hydroxyimino, alower alkanoyloxy-imino, a lower alkylidene, a halogen atom, azido,sulfoxyimino, a group of the formula: ##STR1219## wherein R⁸¹ is ahydrogen atom or a lower alkyl, hydrazino, pyrrolyl, an amino-loweralkanoyloxy having optionally a lower alkyl substituent, a group of theformula: ##STR1220## wherein A is as defined above, and R⁸² and R⁸³ arethe same or different and are each a hydrogen atom, a lower alkyl, acarbamoyl-substituted lower alkyl, a hydroxy-substituted lower alkyl, ora pyridyl-lower alkyl, or R⁸² and R⁸³ may bind together with thenitrogen atom to which they are bonded to form a 5- or 6-memberedsaturated heterocyclic group with or without a second nitrogen atom, anoxygen atom or a sulfur atom wherein said heterocyclic group is selectedfrom the group consisting of pyrrolidinyl, piperidinyl, piperazinyl andmorpholino, and wherein the heterocyclic group has optionally asubstituent selected from oxo, a lower alkyl, a lower alkanoyl, andcarbamoyl, and a group of the formula: ##STR1221## wherein n is asdefined above, and R¹⁴ and R¹⁵ are the same or different and are each ahydrogen atom, a lower alkyl, a lower alkenyl, a lower alkanoyl, acycloalkyl having 3 to 8 carbon atoms, an oxiranyl-substituted loweralkyl, a lower alkyl having 1 to 2 substituents selected from a loweralkoxy, hydroxy and an amino having optionally a lower alkylsubstituent, a phenyl-lower alkyl, a pyridyl-lower alkyl, a loweralkylsulfonyl, benzoyl, a lower alkoxycarbonyl, anilinocarbonyl, anaminocarbonyl having optionally a lower alkyl substituent, acyano-substituted lower alkyl, a lower alkoxycarbonyl-substituted loweralkyl, a carbamoyl-substituted lower alkyl, a carboxy-substituted loweralkyl, a tetrahydropyranyloxy-substituted lower alkyl, a loweralkanoyloxy-substituted lower alkyl, a piperidinyl having optionally aphenyl-lower alkyl substituent on the piperidinyl ring, ahalogen-substituted lower alkanoyl, an imidazolyl-substituted loweralkanoyl, an amino-lower alkanoyl having optionally a substituentselected from a lower alkyl and a lower alkoxycarbonyl, anaminocarbonyl-lower alkyl having optionally a lower alkyl substituent,or a phenyl-lower alkoxycarbonyl, or R¹⁴ and R¹⁵ may bind together withthe nitrogen atom to which they are bonded to form a 5- or 6-memberedsaturated heterocyclic group with or without a second nitrogen atom oran oxygen atom, wherein said heterocyclic group is selected from thegroup consisting of pyrrolidinyl, piperidinyl, piperazinyl andmorpholino, and wherein the heterocyclic group may optionally have asubstituent selected from a lower alkyl, a phenyl-lower alkyl or a loweralkanoyl, and a pharmaceutically acceptable salt thereof.
 55. Thecompound according to claim 53, wherein p in the group: --(CH₂)_(p) --is 3 and the group has no substituent, and a pharmaceutically acceptablesalt thereof.
 56. The compound according to claim 53, wherein p in thegroup: --(CH₂)_(p) -- is 4 and the group has no substituent, and apharmaceutically acceptable salt thereof.
 57. The compound according toclaim 53, wherein p in the group: --(CH₂)_(p) -- is 5, and apharmaceutically acceptable salt thereof.
 58. The compound according toclaim 54, wherein q in the group: --CH═CH--(CH₂)_(q) -- is 1, and apharmaceutically acceptable salt thereof.
 59. The compound according toclaim 54, wherein q in the group: --CH═CH--(CH₂)_(q) -- is 2, and apharmaceutically acceptable salt thereof.
 60. The compound according toclaim 54, wherein q in the group: --CH═CH═(CH₂)_(q) -- is 3, and apharmaceutically acceptable salt thereof.
 61. The compound according toclaim 53 wherein the heterocyclic group of the formula: ##STR1222## is2,3,4,5-tetrahydro-1H-1,4-benzodiazepine, and a pharmaceuticallyacceptable salt thereof. 62.1-[4-(2-Methylbenzoylamino)benzoyl]-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine.63. The compound according to claim 53 wherein the heterocyclic group ofthe formula ##STR1223## is 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine, anda pharmaceutically acceptable salt thereof.